Peroxisome proliferator-activated receptors (PPARs) and the human skin: Importance of PPARs in skin physiology and dermatologic diseases

American Journal of Clinical Dermatology

Volumn 9, Issue 1, 2008, Pages 15-31

  Sertznig, Pit ^a   Seifert, Markus ^a   Tilgen, Wolfgang ^a   Reichrath, Jörg ^a  

^a SAARLAND UNIVERSITY   (Germany)

Author keywords

Atopic dermatitis, treatment; Peroxisome proliferator activated receptor agonists, therapeutic use; Psoriasis, treatment; Skin cancer, general; Thiazolidinediones, therapeutic use

Indexed keywords

2 [1 CARBOXY 2 [4 [2 (5 METHYL 2 PHENYL 4 OXAZOLYL)ETHOXY]PHENYL]ETHYLAMINO]BENZOIC ACID METHYL ESTER; 2 [4 [2 [3 (2,4 DIFLUOROPHENYL) 1 HEPTYLUREIDO]ETHYL]PHENYLTHIO] 2 METHYLPROPIONIC ACID; 2 [4 [2 [3 CYCLOHEXYL 1 (4 CYCLOHEXYLBUTYL)UREIDO]ETHYL]PHENYLTHIO] 2 METHYLPROPIONIC ACID; 2 CHLORO 5 NITRO N (4 PYRIDYL)BENZAMIDE; 2 CHLORO 5 NITROBENZANILIDE; 2,4 THIAZOLIDINEDIONE DERIVATIVE; 3 CHLORO 4 [3 (7 PROPYL 3 TRIFLUOROMETHYLBENZISOXAZOL 6 YLOXY)PROPYLTHIO]PHENYLACETIC ACID; 4 [4 [3 (4 ACETYL 3 HYDROXY 2 PROPYLPHENOXY)PROPOXY]PHENOXY]ACETIC ACID; 5 (2,4 DIOXO 5 THIAZOLIDINYLMETHYL) 2 METHOXY N [4 (TRIFLUOROMETHYL)BENZYL]BENZAMIDE; [2 METHYL 4 [4 METHYL 2 (4 TRIFLUOROMETHYLPHENYL) 5 THIAZOLYLMETHYLTHIO]PHENOXY]ACETIC ACID; [4 [2 (3 FLUORO 4 TRIFLUOROMETHYLPHENYL) 4 METHYL 5 THIAZOLYLMETHYLTHIO] 2 METHYLPHENOXY]ACETIC ACID; AD 5075; ANGIOTENSIN 2 RECEPTOR ANTAGONIST; ANTILIPEMIC AGENT; BEZAFIBRATE; CALCIPOTRIOL; CARBACYCLIN; CIGLITAZONE; CLOFIBRATE; DANA 87; DANA 88; ENGLITAZONE; FARGLITAZAR; FENOFIBRATE; FENOPROFEN; GEMFIBROZIL; GW 0072; GW 2331; GW 2433; GW 2570; GW 409544; GW 6471; IBUPROFEN; INDOMETACIN; L 165461; L 764406; L 796449; L 805645; N (2 BENZOYLPHENYL) O [2 (METHYL 2 PYRIDINYLAMINO)ETHYL]TYROSINE; NETOGLITAZONE; NONSTEROID ANTIINFLAMMATORY AGENT; PALMITIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PIOGLITAZONE; PIRINIXIC ACID; PROSTACYCLIN; REGLITAZAR; ROSIGLITAZONE; SB 219994; TOMELUKAST; TROGLITAZONE; UNINDEXED DRUG; LIGAND;

ACNE VULGARIS; ACTINIC KERATOSIS; AMINO ACID METABOLISM; APOPTOSIS; ATOPIC DERMATITIS; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; CELL DIFFERENTIATION; CELL FUNCTION; CELL GROWTH; CELL PROLIFERATION; CELL SURVIVAL; EPITHELIUM CELL; FUNCTIONS OF THE SKIN AND ITS APPENDAGES; GENE EXPRESSION; GLUCOSE METABOLISM; HUMAN; IMMUNOREACTIVITY; INFLAMMATION; KERATINOCYTE; LIPID METABOLISM; MELANOMA; MELANOMA CELL; MOLECULAR BIOLOGY; NONHUMAN; PHOTOTHERAPY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PSORIASIS; PSORIASIS VULGARIS; REVIEW; SCLERODERMA; SKIN; SKIN ALLERGY; SKIN CANCER; SKIN DISEASE; SKIN FIBROSIS; SKIN INFLAMMATION; SQUAMOUS CELL CARCINOMA; TUMOR GROWTH; VITILIGO; WOUND HEALING; AGONISTS; ANIMAL; GENETICS; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION; SKIN DISEASES; SKIN TUMOR;

ANIMALS; CELL PHYSIOLOGICAL PHENOMENA; GENE EXPRESSION; HUMANS; INFLAMMATION; LIGANDS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; SIGNAL TRANSDUCTION; SKIN DISEASES; SKIN NEOPLASMS; SKIN PHYSIOLOGICAL PHENOMENA; WOUND HEALING;

EID: 47349100516     PISSN: 11750561     EISSN: None     Source Type: Journal    
DOI: 10.2165/00128071-200809010-00002     Document Type: Review

References (228)

1. Wahli W, Braissant O, Desvergne B. Peroxisome proliferator activated receptors: transcriptional regulators of adipogenesis, lipid metabolism and more. Chem Biol 1995; 2: 261-6
2. Desvergne B, Wahli W. PPAR: a key nuclear factor in nutrient/gene interactions? In: Bauerle P, editor. Inducible transcription. Vol. 1. Boston (MA): Birkhäuser, 1995: 142-76
3. Chawla A, Repa JJ, Evans RM, et al. Nuclear receptors and lipid physiology: opening the X-files. Science 2001; 294: 1866-70
4. Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 1999; 20: 649-88
5. Kuenzli S, Saurat JH. Peroxisome proliferator-activated receptors in cutaneous biology. Br J Dermatol 2003; 149: 229-36
6. Escher P, Wahli W. Peroxisome proliferator-activated receptors: insight into multiple cellular functions. Mutat Res 2000; 448: 121-38
7. Gottlicher M, Widmark E, Li Q, et al. Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc Natl Acad Sci U S A 1992; 89: 4653-7
8. Zhu Y, Alvares K, Huang Q, et al. Cloning of a new member of the peroxisome proliferator-activated receptor gene family from mouse liver. J Biol Chem 1993; 268: 26817-20
9. Tontonoz P, Hu E, Graves RA, et al. mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 1994; 8: 1224-34
10. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 1990; 347: 645-50
11. Dreyer C, Krey G, Keller H, et al. Control of the peroxisome beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell 1992; 68: 879-87
12. Amri EZ, Bonino F, Ailhaud G, et al. Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes: homology to peroxisome proliferator-activated receptors. J Biol Chem 1995; 270: 2367-71
13. Chen F, Law SW, O'Malley BW. Identification of two mPPAR related receptors and evidence for the existence of five subfamily members. Biochem Biophys Res Commun 1993; 196: 671-7
14. Kliewer SA, Forman BM, Blumberg B, et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A 1994; 91: 7355-9
15. Sher T, Yi HF, McBride OW, et al. cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator-activated receptor. Biochemistry 1993; 32: 5598-604
16. Greene ME, Blumberg B, McBride OW, et al. Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping. Gene Expr 1995; 4: 281-99
17. Schmidt A, Endo N, Rutledge SJ, et al. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol Endocrinol 1992; 6: 1634-41
18. Lock EA, Mitchell AM, Elcombe CR. Biochemical mechanisms of induction of hepatic peroxisome proliferation. Annu Rev Pharmacol Toxicol 1989; 29: 145-63
19. Guan Y, Zhang Y, Davis L, et al. Expression of peroxisome proliferator-activated receptors in urinary tract of rabbits and humans. Am J Physiol 1997; 273: 1013-22
20. Mukherjee R, Jow L, Noonan D, et al. Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators. J Steroid Biochem Mol Biol 1994; 51: 157-66
21. Beamer BA, Negri C, Yen CJ, et al. Chromosomal localization and partial genomic structure of the human peroxisome proliferator activated receptor-gamma (hPPAR gamma) gene. Biochem Biophys Res Commun 1997; 233: 756-9
22. Takada I, Yu RT, Xu HE, et al. Alteration of a single amino acid in peroxisome proliferator-activated receptor-alpha (PPAR alpha) generates a PPAR delta phenotype. Mol Endocrinol 2000; 14: 733-40
23. Yoshikawa T, Brkanac Z, Dupont BR, et al. Assignment of the human nuclear hormone receptor, NUC1 (PPARD), to chromosome 6p21.1-p21.2. Genomics 1996; 35: 637-8
24. Jones PS, Savory R, Barratt P, et al. Chromosomal localisation, inducibility, tissuespecific expression and strain differences in three murine peroxisome proliferator-activated receptor genes. Eur J Biochem 1995; 233: 219-26
25. Vamecq J, Latruffe N. Medical significance of peroxisome proliferator-activated receptors. Lancet 1999; 354: 141-8
26. Vamecq J, Draye JP. Pathophysiology of peroxisomal beta-oxidation. Essays Biochem 1989; 24: 115-225
27. Forman BM, Tontonoz P, Chen J, et al. 15-deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 1995; 83: 803-12
28. Palmer CN, Hsu MH, Griffin KJ, et al. Novel sequence determinants in peroxisome proliferator signaling. J Biol Chem 1995; 270: 16114-21
29. Varanasi U, Chu R, Huang Q, et al. Identification of a peroxisome proliferator-responsive element upstream of the human peroxisome fatty acyl coenzyme A oxidase gene. J Biol Chem 1996; 271: 2147-55
30. Zhang B, Berger J, Hu E, et al. Negative regulation of peroxisome proliferator-activated receptor-gamma gene expression contributes to the antiadipogenic effects of tumor necrosis factor-alpha. Mol Endocrinol 1996; 10: 1457-66
31. Di-Poï N, Tan NS, Michalik L, et al. Antiapoptotic role of PPARbeta in keratinocytes via transcriptional control of the Akt1 signaling pathway. Mol Cell 2002; 10: 721-33
32. Helledie T, Grøntved L, Jensen SS, et al. The gene encoding the Acyl-CoA-binding protein is activated by peroxisome proliferator-activated receptor gamma through an intronic response element functionally conserved between humans and rodents. J Biol Chem 2002; 277: 26821-30
33. Ghosh S, Singh AK, Aruna B, et al. The genomic organization of mouse resistin reveals major differences from the human resistin: functional implications. Gene 2003; 305: 27-34
34. Palmer CN, Hsu MH, Griffin KJ, et al. Peroxisome proliferator activated receptor-alpha expression in human liver. Mol Pharmacol 1998; 53: 14-22
35. Braissant O, Foufelle F, Scotto C, et al. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, beta, and gamma in the adult rat. Endocrinology 1996; 137: 354-66
36. Auboeuf D, Rieusset J, Fajas L, et al. Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients. Diabetes 1997; 46: 1319-27
37. Gonzalez FJ. The role of peroxisome proliferator activated receptor alpha in peroxisome proliferation, physiological homeostasis, and chemical carcinogenesis. Adv Exp Med Biol 1997; 422: 109-25
38. Escher P, Braissant O, Basu-Modak S, et al. Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding. Endocrinology 2001; 142: 4195-202
39. Michalik L, Desvergne B, Basu-Modak S, et al. Nuclear hormone receptors and mouse skin homeostasis: implication of PPARbeta. Horm Res 2000; 54: 263-8
40. Chawla A, Schwarz EJ, Dimaculangan DD, et al. Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 1994; 135: 798-800
41. Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 1994; 79: 1147-56
42. Fajas L, Auboeuf D, Raspe E, et al. The organization, promotor analysis, and expression of the human PPARgamma gene. J Biol Chem 1997; 272: 18779-89
43. Mansen A, Guardiola-Diaz H, Rafter J, et al. Expression of the peroxisome proliferator-activated receptor (PPAR) in the mouse colonic mucosa. Biochem Biophys Res Commun 1996; 222: 844-51
44. Lefebvre AM, Paulweber B, Fajas L, et al. Peroxisome proliferator- activated receptor gamma is induced during differentiation of colon epithelium cells. J Endocrinol 1999; 162: 331-40
45. Zhu Y, Qi C, Korenberg JR, et al. Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promotor use and different splicing yield two mPPAR gamma isoforms. Proc Natl Acad Sci U S A 1995; 92: 7921-5
46. Fajas L, Fruchart JC, Auwerx J. PPARgamma3 mRNA: a distinct PPARgamma mRNA subtype transcribed from an independent promotor. FEBS Lett 1998; 438: 55-60
47. Auwerx J. PPARgamma, the ultimate thrifty gene. Diabetologia 1999; 42: 1033-49
48. Ricote M, Huang J, Fajas L, et al. Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc Natl Acad Sci U S A 1998; 95: 7614-9
49. Benoit G, Cooney A, Giguere V, et al. International Union of Pharmacology: LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev 2006; 58: 798-836
50. Xu HE, Lambert MH, Montana VG, et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell 1999; 3: 397-403
51. Forman BM, Chen J, Evans RM. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci U S A 1997; 94: 4312-7
52. Yu K, Bayona W, Kallen CB, et al. Differential activation of peroxisome proliferator-activated receptors by eicosanoids. J Biol Chem 1995; 270: 23975-83
53. Westergaard M, Henningsen J, Svendsen ML, et al. Modulation of keratinocyte gene expression and differentiation by PPAR-selective ligands and tetradecylthioacetic acid. J Invest Dermatol 2001; 116: 702-12
54. Dunlop TW, Vaisanen S, Frank C, et al. The human peroxisome proliferator-activated receptor delta gene is a primary target of 1alpha,25-dihydroxyvitamin D3 and its nuclear receptor. J Mol Biol 2005; 349: 248-60
55. Oliver Jr WR, Shenk JL, Snaith MR, et al. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc Natl Acad Sci U S A 2001; 98: 5306-11
56. Gottlicher M, Demoz A, Svensson D, et al. Structural and metabolic requirements for activators of the peroxisome proliferator-activated receptor. Biochem Pharmacol 1993; 46: 2177-84
57. Kliewer SA, Sundseth SS, Jones SA, et al. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci U S A 1997; 94: 4318-23
58. Nagy L, Tontonoz P, Alvarez JG, et al. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. Cell 1998; 93: 229-40
59. Benson SC, Pershadsingh HA, Ho CI, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. Hypertension 2004; 43: 993-1002
60. Schupp M, Janke J, Clasen R, et al. Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. Circulation 2004; 109: 2054-7
61. Sertznig P, Seifert M, Tilgen W, et al. Present concepts and future outlook: function of peroxisome proliferator-activated receptors (PPARs) for pathogenesis, progression and therapy of cancer. J Cell Physiol 2007; 212: 1-12
62. Chen YE, Fu M, Zhang J, et al. Peroxisome proliferator-activated receptors and the cardiovascular system. Vitam Horm 2003; 66: 157-88
63. Ibabe A, Herrero A, Cajaraville MP. Modulation of peroxisome proliferator-activated receptors (PPARs) by PPAR(alpha)- and PPAR(gamma)-specific ligands and by 17beta-estradiol in isolated zebrafish hepatocytes. Toxicol In Vitro 2005; 19: 725-35
64. Kliewer SA, Xu HE, Lambert MH, et al. Peroxisome proliferator-activated receptors: from genes to physiology. Recent Prog Horm Res 2001; 56: 239-63
65. Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med 2002; 53: 409-35
66. Willson TM, Brown PJ, Sternbach DD, et al. The PPARs: from orphan receptors to drug discovery. J Med Chem 2000; 43: 527-50
67. Lehmann JM, Lenhard JM, Oliver BB, et al. Peroxisome proliferator- activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem 1997; 272: 3406-10
68. Berger J, Bailey P, Biswas C, et al. Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-gamma: binding and activation correlate with antidiabetic actions in db/db mice. Endocrinology 1996; 137: 4189-95
69. Lehmann JM, Moore LB, Smith-Oliver TA, et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator- activated receptor gamma (PPAR gamma). J Biol Chem 1995; 270: 12953-6
70. Willson TM, Cobb JE, Cowan DJ, et al. The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem 1996; 39: 665-8
71. Kim M, Jeong S, Song YH, et al. Two synthetic ligands for peroxisome proliferator-activated receptor gamma. J Biomed Lab Sci 2004; 10: 137-42
72. Yamanouchi T. KRP-297, MCC-555. Nippon Rinsho 2001; 59: 2200-6
73. Huang JT, Welch JS, Ricote M, et al. Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase. Nature 1999; 400: 378-82
74. Delerive P, Furman C, Teissier E, et al. Oxidized phospholipids activate PPARalpha in a phospholipase A2-dependent manner. FEBS Lett 2000; 471: 34-8
75. Guzman M, Lo Verme J, Fu J, et al. Oleoylethanolamide stimulates lipolysis by activating the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR-alpha). J Biol Chem 2004; 279: 27849-54
76. Chintharlapalli S, Papineni S, Konopleva M, et al. 2-cyano-3,12- dioxoolean-1,9-dien-28-oic acid and related compounds inhibit growth of colon cancer cells through peroxisome proliferator-activated receptor gamma-dependent and -independent pathways. Mol Pharmacol 2005; 68 (1): 119-28
77. Berger J, Leibowitz MD, Doebber TW, et al. Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem 1999; 274: 6718-25
78. Fehlberg S, Gregel CM, Goke A, et al. Bisphenol A diglycidyl ether-induced apoptosis involves Bax/Bid-dependent mitochondrial release of apoptosis-inducing factor (AIF), cytochrome c and Smac/DIABLO. Br J Pharmacol 2003; 139: 495-500
79. Rocchi S, Picard F, Vamecq J, et al. A unique PPARgamma ligand with potent insulin-sensitizing yet weak adipogenic activity. Mol Cell 2001; 8: 737-47
80. Heppner TJ, Bonev AD, Eckman DM, et al. Novel PPARgamma agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries. Pharmacology 2005; 73: 15-22
81. Bishop-Bailey D, Warner TD. PPARgamma ligands induce prostaglandin production in vascular smooth muscle cells: indomethacin acts as a peroxisome proliferator-activated receptor-gamma antagonist. FASEB J 2003; 17: 1925-7
82. Trivedi NR, Cong Z, Nelson AM, et al. Peroxisome proliferator-activated receptors increase human sebum production. J Invest Dermatol 2006; 126: 2002-9
83. Brown PJ, Smith-Oliver TA, Charifson PS, et al. Identification of peroxisome proliferator-activated receptor ligands from a biased chemical library. Chem Biol 1997; 4: 909-18
84. Mossner R, Meyer P, Jankowski F, et al. Variations in the peroxisome proliferator-activated receptor-gamma gene and melanoma risk. Cancer Lett 2007; 246: 218-23
85. Xu HE, Stanley TB, Montana VG, et al. Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha. Nature 2002; 415: 813-7
86. Brown PJ, Stuart LW, Hurley KP, et al. Identification of a subtype selective human PPARalpha agonist through parallel-array synthesis. Bioorg Med Chem Lett 2001; 11: 1225-7
87. Brown PJ, Winegar DA, Plunket KD, et al. A ureido-thioisobutyric acid (GW9578) is a subtype-selective PPARalpha agonist with potent lipid-lowering activity. J Med Chem 1999; 42: 3785-8
88. Miyahara T, Schrum L, Rippe R, et al. Peroxisome proliferator-activated receptors and hepatic stellate cell activation. J Biol Chem 2000; 275: 35715-22
89. Collin M, Murch O, Thiemermann C. Peroxisome proliferator-activated receptor-gamma antagonists GW9662 and T0070907 reduce the protective effects of lipopolysaccharide preconditioning against organ failure caused by endotoxemia. Crit Care Med 2006; 34 (4): 1131-8
90. Xu HE, Lambert MH, Montana VG, et al. Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A 2001; 98: 13919-24
91. Debril MB, Renaud JP, Fajas L, et al. The pleiotropic functions of peroxisome proliferator-activated receptor gamma. J Mol Med 2001; 79: 30-47
92. Leibowitz MD, Fievet C, Hennuyer N, et al. Activation of PPARdelta alters lipid metabolism in db/db mice. FEBS Lett 2000; 473: 333-6
93. Elbrecht A, Chen Y, Adams A, et al. L-764406 is a partial agonist of human peroxisome proliferator-activated receptor gamma: the role of Cys313 in ligand binding. J Biol Chem 1999; 274: 7913-22
94. Berger J, Tanen M, Elbrecht A, et al. Peroxisome proliferator-activated receptor-gamma ligands inhibit adipocyte 11beta-hydroxysteroid dehydrogenase type 1 expression and activity. J Biol Chem 2001; 276: 12629-35
95. Panchapakesan U, Pollock CA, Chen XM. The effect of high glucose and PPAR-gamma agonists on PPAR-gamma expression and function in HK-2 cells. Am J Physiol Renal Physiol 2004; 287: 528-34
96. White IR, Man WJ, Bryant D, et al. Protein expression changes in the Sprague Dawley rat liver proteome following administration of peroxisome proliferator activated receptor alpha and gamma ligands. Proteomics 2003; 3: 505-12
97. Jarvis MC, Gray TJ, Palmer CN. Both PPARgamma and PPARdelta influence sulindac sulfide-mediated p21WAF1/CIP1 upregulation in a human prostate epithelial cell line. Oncogene 2005; 24: 8211-5
98. Keller H, Dreyer C, Medin J, et al. Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers. Proc Natl Acad Sci U S A 1993; 90: 2160-4
99. Tugwood JD, Issemann I, Anderson RG, et al. The mouse peroxisome proliferator activated receptor recognizes a response element in the 5′flanking sequence of the rat acyl CoA oxidase gene. EMBO J 1992; 11: 433-9
100. Zhang B, Marcus SL, Sajjadi FG, et al. Identification of a peroxisome proliferator-responsive element upstream of the gene encoding rat peroxisome enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase. Proc Natl Acad Sci U S A 1992; 89: 7541-5
101. Gulick T, Cresci S, Caira T, et al. The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression. Proc Natl Acad Sci U S A 1994; 91: 11012-6
102. Schoonjans K, Watanabe M, Suzuki H, et al. Induction of the acyl-coenzyme A synthetase gene by fibrates and fatty acids is mediated by a peroxisome proliferator response element in the C promoter. J Biol Chem 1995; 270: 19269-76
103. Muerhoff AS, Griffin KJ, Johnson EF. The peroxisome proliferator- activated receptor mediates the induction of CYP4A6, a cytochrome P450 fatty acid omega-hydroxylase, by clofibric acid. J Biol Chem 1992; 267: 19051-3
104. Rodriguez JC, Gil-Gomez G, Hegardt FG, et al. Peroxisome proliferator-activated receptor mediates induction of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by fatty acids. J Biol Chem 1994; 269: 18767-72
105. Vu-Dac N, Schoonjans K, Laine B, et al. Negative regulation of the human apolipoprotein A-I promoter by fibrates can be attenuated by the interaction of the peroxisome proliferator-activated receptor with its response element. J Biol Chem 1994; 269: 31012-8
106. Vu-Dac N, Schoonjans K, Kosykh V, et al. Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. J Clin Invest 1995; 96: 741-50
107. Hertz R, Bishara-Shieban J, Bar-Tana J. Mode of action of peroxisome proliferators as hypolipidemic drugs: suppression of apolipoprotein C-III. J Biol Chem 1995; 270: 13470-5
108. Staels B, Koenig W, Habib A, et al. Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature 1998; 393: 790-3
109. Linton MF, Fazio S. Re-emergence of fibrates in the management of dyslipidaemia and cardiovascular risk. Curr Atheroscler Rep 2000; 2: 29-35
110. Rubins HB, Robins SJ. Conclusions from the VA-HIT study. Am J Cardiol 2000; 86: 543-4
111. Bastie C, Luquet S, Holst D, et al. Alterations of peroxisome proliferator-activated receptor delta activity affect fatty acid-controlled adipose differentiation. J Biol Chem 2000; 275: 38768-73
112. Bastie C, Holst D, Gaillard D, et al. Expression of peroxisome proliferator-activated receptor PPARdelta promotes induction of PPARgamma and adipocyte differentiation in 3T3C2 fibroblasts. J Biol Chem 1999; 274: 21920-5
113. Hansen JB, Zhang H, Rasmussen TH, et al. Peroxisome proliferator- activated receptor delta (PPARdelta)-mediated regulation of preadipocyte proliferation and gene expression is dependent on cAMP signaling. J Biol Chem 2001; 276: 3175-82
114. Jehl-Pietri C, Bastie C, Gillot I, et al. Peroxisome-proliferator- activated receptor delta mediates the effects of long-chain fatty acids on post-confluent cell proliferation. Biochem J 2000; 350: 93-8
115. Kim DJ, Akiyama TE, Harman FS, et al. Peroxisome proliferator-activated receptor beta (delta)-dependent regulation of ubiquitin C expression contributes to attenuation of skin carcinogenesis. J Biol Chem 2004; 279: 23719-27
116. Basu-Modak S, Braissant O, Escher P, et al. Peroxisome proliferator-activated receptor beta regulates acyl-CoA synthetase 2 in reaggregated rat brain cell cultures. J Biol Chem 1999; 274: 35881-8
117. Saluja I, Granneman JG, Skoff RP. PPAR delta agonists stimulate oligodendrocyte differentiation in tissue culture. Glia 2001; 33: 191-204
118. Granneman J, Skoff R, Yang X. Member of the peroxisome proliferator-activated receptor family of transcription factors is differentially expressed by oligodendrocytes. J Neurosci Res 1998; 51: 563-73
119. Peters JM, Lee SS, Li W, et al. Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). Mol Cell Biol 2000; 20: 5119-28
120. Mano H, Kimura C, Fujisawa Y, et al. Cloning and function of rabbit peroxisome proliferator-activated receptor delta/beta in mature osteoclasts. J Biol Chem 2000; 275: 8126-32
121. Son C, Hosoda K, Matsuda J, et al. Up-regulation of uncoupling protein 3 gene expression by fatty acids and agonists for PPARs in L6 myotubes. Endocrinology 2001; 142: 4189-94
122. Matsuda J, Hosoda K, Itoh H, et al. Cloning of rat uncoupling protein-3 and uncoupling protein-2 cDNAs: their gene expression in rats fed high-fat diet. FEBS Lett 1997; 418: 200-4
123. Zurlo F, Larson K, Bogardus C, et al. Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Invest 1990; 86: 1423-7
124. Lim H, Gupta RA, Ma WG, et al. Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta. Genes Dev 1999; 13: 1561-74
125. Clark RB. The role of PPARs in inflammation and immunity. J Leukoc Biol 2002; 71: 388-400
126. Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes 1998; 47: 507-14
127. Spiegelman BM, Flier JS. Obesity and the regulation of energy balance. Cell 2001; 104: 531-43
128. Rosen ED, Spiegelman BM. PPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 2001; 276: 37731-4
129. Barak Y, Nelson MC, Ong ES, et al. PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell 1999; 4: 585-95
130. Rosen ED, Walkey CJ, Puigserver P, et al. Transcriptional regulation of adipogenesis. Genes Dev 2000; 14: 1293-307
131. Frohnert BI, Hui TY, Bernlohr DA. Identification of a functional peroxisome proliferator-responsive element in the murine fatty acid transport protein gene. J Biol Chem 1999; 274: 3970-7
132. Schonjans K, Peinado-Onsurbe J, Lefebvre AM, et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 1996; 15: 5336-48
133. Tontonoz P, Hu E, Devine J, et al. PPAR gamma 2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol 1995; 15: 351-7
134. Miller CW, Ntambi JM. Peroxisome proliferators induce mouse liver stearoyl-CoA desaturase 1 gene expression. Proc Natl Acad Sci USA 1996; 93: 9443-8
135. Thomson B, Ahrens JM, Ntambi JM, et al. 2-methylene-19-nor-1alpha- hydroxyvitamin D3 analogs inhibit adipocyte differentiation and PPARgamma2 gene transcription. Arch Biochem Biophys 2007; 460: 192-201
136. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993; 259: 87-91
137. Hotamisligil GS, Murray DL, Choy LN, et al. Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci U S A 1994; 91: 4854-8
138. Hofmann C, Lorenz K, Braithwaite SS, et al. Altered gene expression for tumor necrosis factor-alpha and its receptors during drug and dietary modulation of insulin resistance. Endocrinology 1994; 134: 264-70
139. Miles PD, Romeo OM, Higo K, et al. TNF-alpha-induced insulin resistance in vivo and its prevention by troglitazone. Diabetes 1997; 46: 1678-83
140. Peraldi P, Xu M, Spiegelman BM. Thiazolidinediones block tumor necrosis factor-alpha-induced inhibition of insulin signaling. J Clin Invest 1997; 100: 1863-9
141. Chinetti G, Griglio S, Antonucci M, et al. Activation of proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages. J Biol Chem 1998; 273: 25573-80
142. Su CG, Wen X, Bailey ST, et al. A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response. J Clin Invest 1999; 104: 383-9
143. Nijsten T, Colpaert CG, Vermeulen PB, et al. Cyclooxygenase-2 expression and angiogenesis in squamous cell carcinoma of the skin and its precursors: a paired immunohistochemical study of 35 cases. Br J Dermatol 2001; 151: 837-45
144. Gelman L, Fruchart JC, Auwerx J. An update on the mechanisms of action of the peroxisome proliferator-activated receptors (PPARs) and their roles in inflammation and cancer. Cell Mol Life Sci 1999; 55: 932-43
145. Houseknecht KL, Cole BM, Steele PJ. Peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligands: a review. Domest Anim Endocrinol 2002; 22: 1-23
146. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature 2000; 405: 421-4
147. Wahli W. Peroxisome proliferator-activated receptors (PPARs): from metabolic control to epidermal wound healing. Swiss Med Wkly 2002; 132: 83-91
148. Michalik L, Desvergne B, Tan NS, et al. Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPARbeta mutant mice. J Cell Biol 2001; 154: 799-814
149. Braissant O, Wahli W. Differential expression of peroxisome proliferator-activated receptor-alpha, -beta, and -gamma during rat embryonic development. Endocrinology 1998; 139: 2748-54
150. Matsuura H, Adachi H, Smart RC, et al. Correlation between expression of peroxisome proliferator-activated receptor beta and squamous differentiation in epidermal and tracheobronchial epithelial cells. Mol Cell Endocrinol 1999; 147: 85-92
151. Rosenfield RL, Kentsis A, Deplewski D, et al. Rat preputial sebocyte differentiation involves peroxisome proliferator-activated receptors. J Invest Dermatol hepato1999; 112: 226-32
152. Hanley K, Jiang Y, He SS, et al. Keratinocyte differentiation is stimulated by activators of the nuclear receptor PPARalpha. J Invest Dermatol 1998; 110: 368-75
153. Rivier M, Safonova I, Lebrun P, et al. Differential expression of peroxisome proliferator-activated receptor subtypes during the differentiation of human keratinocytes. J Invest Dermatol 1998; 111: 1116-21
154. Westergaard M, Henningsen J, Johansen C, et al. Expression and localization of peroxisome proliferator-activated receptors and nuclear factor kappaB in normal and lesional psoriatic skin. J Invest Dermatol 2003; 121: 1104-17
155. Mossner R, Schulz U, Kruger U, et al. Agonists of peroxisome proliferator-activated receptor gamma inhibit cell growth in malignant melanoma. J Invest Dermatol 2002; 119: 576-82
156. Nijsten T, Geluyckens E, Colpaert C, et al. Peroxisome proliferator-activated receptors in squamous cell carcinoma and its precursors. J Cutan Pathol 2005; 32: 340-7
157. Schmuth M, Elias PM, Feingold KR. Beyond glucocorticoids, retinoids and vitamin D: the evolution of nuclear hormone type transcription factor targeting in the skin. J Dtsch Dermatol Ges 2003; 1: 352-62
158. Pineau T, Hudgins WR, Liu L, et al. Activation of a human peroxisome proliferator-activated receptor by the antitumor agent phenylacetate and its analogs. Biochem Pharmacol 1996; 52: 659-67
159. Rivier M, Castiel I, Safonova I, et al. Peroxisome proliferator-activated receptor-alpha enhances lipid metabolism in a skin equivalent model. J Invest Dermatol 2000; 114: 681-7
160. Hanley K, Jiang Y, Crumrine D, et al. Activators of the nuclear hormone receptors PPARalpha and FXR accelerate the development of the fetal epidermal permeability barrier. J Clin Invest 1997; 100: 705-12
161. Billoni N, Buan B, Gautier B, et al. Expression of peroxisome proliferator activated receptors (PPARs) in human hair follicles and PPAR alpha involvement in hair growth. Acta Derm Venereol 2000; 80: 329-34
162. Rosenfield RL, Deplewski D, Greene ME. Peroxisome proliferator-activated receptors and skin development. Horm Res 2000; 54: 269-74
163. Kang HY, Chung E, Lee M, et al. Expression and function of peroxisome proliferator-activated receptors in human melanocytes. Br J Dermatol 2004; 150: 462-8
164. Lee JS, Choi YM, Kang HY. PPAR-gamma agonist, ciglitazone, increases pigmentation and migration of human melanocytes. Exp Dermatol 2007; 16: 118-23
165. Serhan C, Chiang N. Novel endogenous small molecules as the checkpoint controllers in inflammation and resolution: entree for resoleomics. Rheum Dis Clin North Am 2004; 30: 69-95
166. Schilling JA. Wound healing. Surg Clin North Am 1976; 56: 859-74
167. Tan NS, Michalik L, Noy N, et al. Critical roles of PPAR beta/delta in keratinocyte response to inflammation. Genes Dev 2001; 15: 3263-77
168. Beier K, Volkl A, Fahimi HD. TNF-alpha downregulates the peroxisome proliferator activated receptor-alpha and the mRNAs encoding peroxisomal protein in rat liver. FEBS Lett 1997; 412: 385-7
169. Grose R, Werner S. An aPPARently protective mechanism for keratinocytes in wounded skin. Trends Mol Med 2002; 8: 149-51
170. Devchand PR, Keller H, Peters JM, et al. The PPARalpha-leukotriene B4 pathway to inflammation control. Nature 1996; 384: 39-43
171. Wenzel SE. New approaches to anti-inflammatory therapy for asthma. Am J Med 1998; 104: 287-300
172. Greenspan PD, Fujimoto RA, Marshall PJ, et al. Carboxy-substituted cinnamides: a novel series of potent orally active LTB4 receptor antagonists. J Med Chem 1999; 42: 164-72
173. Komuves LG, Hanley K, Man MQ, et al. Keratinocyte differentiation in hyperproliferative epidermis: topical application of PPARalpha activators restores tissue homeostasis. J Invest Dermatol 2000; 115: 361-7
174. Komuves LG, Hanley K, Lefebvre AM, et al. Stimulation of PPARalpha promotes epidermal keratinocyte differentiation in vivo. J Invest Dermatol 2000; 115: 353-60
175. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A 1993; 90: 7915-22
176. Hong JT, Glauert HP. Stimulation of the DNA binding activity of AP-1 by the peroxisome proliferator ciprofibrate and eicosanoids in cultured rat hepatocytes. Toxicology 1998; 131: 99-107
177. Johannes CB, Stellato RK, Feldman HA, et al. Relation of dehydroepiandrosterone and dehydroepiandrosterone sulfate with cardiovascular disease risk factors in women: longitudinal results from the Massachusetts Women's Health Study. J Clin Epidemiol 1999; 52: 95-103
178. Palmer CN, Causevic M, Wolf CR. Modulation of fatty acid signalling by cytochrome P-450-mediated hydroxylation. Biochem Soc Trans 1997; 25: 1160-5
179. Zhou YC, Waxman DJ. Cross-talk between janus kinase-signal transducer and activator of transcription (JAK-STAT) and peroxisome proliferator-activated receptor-alpha (PPARalpha) signaling pathways: growth hormone inhibition of PPARalpha transcriptional activity mediated by stat5b. J Biol Chem 1999; 274: 2672-81
180. Poynter ME, Daynes RA. Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-kappaB signaling, and reduces inflammatory cytokine production in aging. J Biol Chem 1998; 273: 32833-41
181. Waxman DJ. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch Biochem Biophys 1999; 369: 11-23
182. de Moissac D, Zheng H, Kirshenbaum LA. Linkage of the BH4 domain of Bcl-2 and nuclear factor kappaB signaling pathway for suppression of apoptosis. J Biol Chem 1999; 274: 29505-9
183. Pikarsky E, Porat RM, Stein I, et al. NF-kappaB functions as a tumour promotor in inflammation-associated cancer. Nature 2004; 431: 461-6
184. Kippenberger S, Loitsch SM, Grundmann-Kollmann M, et al. Activators of peroxisome proliferator-activated receptors protect human skin from ultraviolet-B-light-induced inflammation. J Invest Dermatol 2001; 117: 1430-6
185. Sheu MY, Fowler AJ, Kao J, et al. Topical peroxisome proliferator activated receptor-alpha activators reduce inflammation in irritant and allergic contact dermatitis models. J Invest Dermatol 2002; 118: 94-101
186. Gniadecki R, Calverley MJ. Emerging drugs in psoriasis. Expert Opin Emerg Drugs 2002; 7: 69-90
187. Ellis CN, Varani J, Fisher GJ, et al. Troglitazone improves psoriasis and normalizes models of proliferative skin disease: ligands for peroxisome proliferator-activated receptor-gamma inhibit keratinocyte proliferation. Arch Dermatol 2000; 136: 609-16
188. Plager DA, Leontovich AA, Henke SA, et al. Early cutaneous gene transcription changes in adult atopic dermatitis and potential clinical implications. Exp Dermatol 2007; 16: 28-36
189. Robertshaw H, Friedmann PS. Pioglitazone: a promising therapy for psoriasis. Br J Dermatol 2005; 152: 189-91
190. Krentz AJ, Bailey CJ, Melander A. Thiazolidinediones for type 2 diabetes: new agents reduce insulin resistance but need long term clinical trials. BMJ 2000; 321: 252-3
191. Sarraf P, Mueller E, Jones D, et al. Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat Med 1998; 4: 1046-52
192. Elstner E, Müller C, Koshizuka K, et al. Ligands for peroxisome proliferator-activated receptor-gamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci U S A 1998; 95 (15): 8806-11
193. Heaney AP, Fernando M, Melmed S. PPAR-gamma receptor ligands: novel therapy for pituitary adenomas. J Clin Invest 2003; 111 (9): 1381-8
194. Motomura W, Okumura T, Takahashi N, et al. Activation of peroxisome proliferator-activated receptor gamma by troglitazone inhibits cell growth through the increase of p27KiP1 in human pancreatic carcinoma cells. Cancer Res 2000; 60 (19): 5558-64
195. Hashimoto Y, Shimada Y, Itami A, et al. Growth inhibition through activation of peroxisome proliferator-activated receptor gamma in human oesophageal squamous cell carcinoma. Eur J Cancer 2003; 39 (15): 2239-46
196. Komuves LG, Hanley K, Man MQ, et al. Keratinocyte differentiation in hyperproliferative epidermis: topical application of PPARalpha activators restores tissue homeostasis. J Invest Dermatol 2000; 115: 361-7
197. Komuves LG, Hanley K, Lefebvre AM, et al. Stimulation of PPARalpha promotes epidermal keratinocyte differentiation in vivo. J Invest Dermatol 2000; 115: 353-60
198. Thuillier P, Anchiraico GJ, Nickel KP, et al. Activators of peroxisome proliferator-activated receptor-alpha partially inhibit mouse skin tumor promotion. Mol Carcinog 2000; 29: 134-42
199. Kopelovich L, Fay JR, Glazer RI, et al. Peroxisome proliferator-activated receptor modulators as potential chemopreventive agents. Mol Cancer Ther 2002; 1: 357-63
200. Theocharis S, Kanelli H, Politi E, et al. Expression of peroxisome proliferator-activated receptor-gamma in non-small cell lung carcinoma: correlation with histological type and grade. Lung Cancer 2002; 36: 249-55
201. Han SW, Greene ME, Pitts J, et al. Novel expression and function of peroxisome proliferator-activated receptor gamma (PPARgamma) in human neuroblastoma cells. Clin Cancer Res 2001; 7: 98-104
202. Di-Poi N, Michalik L, Tan NS, et al. The anti-apoptotic role of PPARbeta contributes to efficient skin wound healing. J Steroid Biochem Mol Biol 2003; 85: 257-65
203. Margeli A, Kouraklis G, Theocharis S. Peroxisome proliferator activated receptor gamma (PPAR-gamma) ligands and angiogenesis. Angiogenesis 2003; 6: 165-9
204. Jaeckel EC, Raja S, Tan J, et al. Correlation of expression of cyclooxygenase-2, vascular endothelial growth factor, and peroxisome proliferator-activated receptor delta with head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2001; 127: 1253-9
205. Muller-Decker K, Reinerth G, Krieg P, et al. Prostaglandin-H-synthase isozyme expression in normal and neoplastic skin. Int J Cancer 1999; 82: 648-56
206. Chinetti G, Lestavel S, Bocher V, et al. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med 2001; 7: 23-4
207. Michalik L, Desvergne B, Wahli W. Peroxisome proliferator-activated receptors and cancers: complex stories. Nat Rev Cancer 2004; 4: 61-70
208. Marks F, Furstenberger G. Cancer chemoprevention through interruption of multistage carcinogenesis: the lessons learnt by comparing mouse skin carcinogenesis and human large bowel cancer. Eur J Cancer 2000; 36: 314-29
209. Diepgen TL, Mahler V. The epidemiology of skin cancer. Br J Dermatol 2002; 146: 1-6
210. Jemal A, Tiwari RC, Murray T, et al. Cancer statistics, 2004. CA Cancer J Clin 2004; 54: 8-29
211. Freudlsperger C, Moll I, Schumacher U, et al. Anti-proliferative effect of peroxisome proliferator-activated receptor gamma agonists on human malignant melanoma cells in vitro. Anticancer Drugs 2006; 17: 325-32
212. Grabacka M, Plonka PM, Urbanska K, et al. Peroxisome proliferator- activated receptor alpha activation decreases metastatic potential of melanoma cells in vitro via down-regulation of Akt. Clin Cancer Res 2006; 12: 3028-36
213. Grabacka M, Placha W, Plonka PM, et al. Inhibition of melanoma metastases by fenofibrate. Arch Dermatol Res 2004; 296: 54-8
214. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol: Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 341: 410-8
215. Ghosh AK, Bhattacharyya S, Lakos G, et al. Disruption of transforming growth factor beta signaling and profibrotic responses in normal skin fibroblasts by peroxisome proliferator-activated receptor gamma. Arthritis Rheum 2004; 50: 1305-18
216. Nestel PJ. Effects of N-3 fatty acids on lipid metabolism. Annu Rev Nutr 1990; 10: 149-67
217. Fisher GJ, Voorhees JJ. Molecular mechanisms of photoaging and its prevention by retinoic acid: ultraviolet irradiation induces MAP kinase signal transduction cascades that induce Ap-1-regulated matrix metalloproteinases that degrade human skin in vivo. J Invest Dermatol Symp Proc 1998; 3: 61-8
218. Kang WH, Chun SC, Lee S. Intermittent therapy for melasma in Asian patients with combined topical agents (retinoic acid, hydroquinone and hydrocortisone): clinical and histological studies. J Dermatol 1998; 25: 587-96
219. Parsad D, Saini R, Verma N. Combination of PUVAsol and topical calcipotriol in vitiligo. Dermatology 1998; 197: 167-70
220. Ameen M, Exarchou V, Chu AC. Topical calcipotriol as monotherapy and in combination with psoralen plus ultraviolet A in the treatment of vitiligo. Br J Dermatol 2001; 145: 476-9
221. Chiaverini C, Passeron T, Ortonne JP. Treatment of vitiligo by topical calcipotriol. J Eur Acad Dermatol Venereol 2002; 16: 137-8
222. Nagai K, Ichimiya M, Yokoyama K, et al. Successful treatment of non-segmental vitiligo: systemic therapy with sex hormone-thyroid powder mixture. Horm Res 2000; 54: 316-7
223. Chen W, Yang CC, Sheu HM, et al. Expression of peroxisome proliferator-activated receptor and CCAAT/enhancer binding protein transcription factors in cultured human sebocytes. J Invest Dermatol 2003; 121: 441-7
224. Sato H, Ishihara S, Kawashima K, et al. Expression of peroxisome proliferator-activated receptor (PPAR)gamma in gastric cancer and inhibitory effects of PPARgamma agonists. Br J Cancer 2000; 83: 1394-400
225. Weindl G, Schafer-Korting M, Schaller M, et al. Peroxisome proliferator-activated receptors and their ligands: entry into the post-glucocorticoid era of skin treatment? Drugs 2005; 65: 1919-34
226. Krentz AJ, Friedmann PS. Type 2 diabetes, psoriasis and thiazolidinediones. Int J Clin Pract 2006; 60: 362-3
227. Panigrahy D, Huang S, Kieran MW, et al. PPARgamma as a therapeutic target for tumor angiogenesis and metastasis. Cancer Biol Ther 2005; 4: 687-93
228. Thies A, Nugel D, Pfuller U, et al. Influence of mistletoe lectins and cytokines induced by them on cell proliferation of human melanoma cells in vitro. Toxicology 2005; 207: 105-16