The role of TGF-β in polycystic ovary syndrome

Reproductive Sciences

Volumn 21, Issue 1, 2014, Pages 20-31

  Raja Khan, Nazia ^a   Urbanek, Margrit ^b   Rodgers, Raymond J ^c   Legro, Richard S ^a  

^a PENN STATE COLLEGE OF MEDICINE   (United States)

^b NORTHWESTERN UNIVERSITY   (United States)

^c UNIVERSITY OF ADELAIDE   (Australia)

Author keywords

fetal origins; fibrillin; genetics; polycystic ovary syndrome; TGF

Indexed keywords

ALDOSTERONE; BONE MORPHOGENETIC PROTEIN 15; C REACTIVE PROTEIN; CONNECTIVE TISSUE GROWTH FACTOR; FIBRILLIN 1; FOLLISTATIN; GROWTH DIFFERENTIATION FACTOR 9; INSULIN; LATENT TRANSFORMING GROWTH FACTOR BETA BINDING PROTEIN; LOSARTAN; ROSIGLITAZONE; TESTOSTERONE; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2;

ACVR1 GENE; AMH GENE; AMHR GENE; ANOVULATION; AORTA ANEURYSM; AORTA DISSECTION; ARTERY DISEASE; BONE MORPHOGENETIC GENE 15; CARDIOVASCULAR RISK; DIATHERMY; EXTRACELLULAR MATRIX; FEMALE; FETUS; FIBRILLIN 1 GENE; FIBRILLIN 3 GENE; FOLLISTATIN GENE; GENE; GENE LOCUS; GENE MAPPING; GENE MUTATION; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC VARIABILITY; GROWTH DIFFERENTIATION FACTOR 9 GENE; HIRSUTISM; HUMAN; HYPERANDROGENISM; HYPERTENSION; IMPAIRED GLUCOSE TOLERANCE; INSULIN RESISTANCE; LASER SURGERY; MARFAN SYNDROME; NON INSULIN DEPENDENT DIABETES MELLITUS; OVARY POLYCYSTIC DISEASE; PHENOTYPE; PRIORITY JOURNAL; PROGENY; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SIGNAL TRANSDUCTION; VASOCONSTRICTION; WEDGE RESECTION;

FETAL ORIGINS; FIBRILLIN; GENETICS; POLYCYSTIC OVARY SYNDROME; TGF-Β;

ANIMALS; FEMALE; FERTILITY; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; HUMANS; INFERTILITY, FEMALE; MICROFILAMENT PROTEINS; OVARY; PHENOTYPE; POLYCYSTIC OVARY SYNDROME; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA;

EID: 84890281400     PISSN: 19337191     EISSN: 19337205     Source Type: Journal    
DOI: 10.1177/1933719113485294     Document Type: Review

References (114)

1. Raja-Khan N, Legro RS. Diagnosis and management of polycystic ovary syndrome. J Clin Outcomes Manage. 2005 ; 12 (4). 218-227
2. Urbanek M, Legro RS, Driscoll DA, et al. Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. Proc Natl Acad Sci U S A. 1999 ; 96 (15). 8573-8578
3. Urbanek M, Woodroffe A, Ewens KG, et al. Candidate gene region for polycystic ovary syndrome on chromosome 19p13.2. J Clin Endocrinol Metab. 2005 ; 90 (12). 6623-6629
4. Stewart DR, Dombroski BA, Urbanek M, et al. Fine mapping of genetic susceptibility to polycystic ovary syndrome on chromosome 19p13.2 and tests for regulatory activity. J Clin Endocrinol Metab. 2006 ; 91 (10). 4112-4117
5. Fornoni A, Lenz O, Striker LJ, Striker GE. Glucose induces clonal selection and reversible dinucleotide repeat expansion in mesangial cells isolated from glomerulosclerosis-prone mice. Diabetes. 2003 ; 52 (10). 2594-2602
6. Ferrand PE, Parry S, Sammel M, et al. A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans. Mol Hum Reprod. 2002 ; 8 (5). 494-501
7. Fenech AG, Billington CK, Swan C, et al. Novel polymorphisms influencing transcription of the human CHRM2 gene in airway smooth muscle. Am J Respir Cell Mol Biol. 2004 ; 30 (5). 678-686
8. Dolan-O'Keefe M, Chow V, Monnier J, Visner GA, Nick HS. Transcriptional regulation and structural organization of the human cytosolic phospholipase A(2) gene. Am J Physiol Lung Cell Mol Physiol. 2000 ; 278 (4). L649-657
9. Huang X, Vaag A, Carlsson E, Hansson M, Ahren B, Groop L. Impaired cathepsin L gene expression in skeletal muscle is associated with type 2 diabetes. Diabetes. 2003 ; 52 (9). 2411-2418
10. Hata R, Akai J, Kimura A, Ishikawa O, Kuwana M, Shinkai H. Association of functional microsatellites in the human type I collagen alpha2 chain (COL1A2) gene with systemic sclerosis. Biochem Biophys Res Commun. 2000 ; 272 (1). 36-40
11. Rothenburg S, Koch-Nolte F, Rich A, Haag F. A polymorphic dinucleotide repeat in the rat nucleolin gene forms Z-DNA and inhibits promoter activity. Proc Natl Acad Sci U S A. 2001 ; 98 (16). 8985-8990
12. Gebhardt F, Zanker KS, Brandt B. Modulation of epidermal growth factor receptor gene transcription by a polymorphic dinucleotide repeat in intron 1. J Biol Chem. 1999 ; 274 (19). 13176-13180
13. Gabellini N. A polymorphic GT repeat from the human cardiac Na+Ca2+ exchanger intron 2 activates splicing. Eur J Biochem. 2001 ; 268 (4). 1076-1083
14. Hui J, Stangl K, Lane WS, Bindereif A. HnRNP L stimulates splicing of the eNOS gene by binding to variable-length CA repeats. Nat Struct Biol. 2003 ; 10 (1). 33-37
15. Hui J, Reither G, Bindereif A. Novel functional role of CA repeats and hnRNP L in RNA stability. RNA. 2003 ; 9 (8). 931-936
16. Stangl K, Cascorbi I, Laule M, et al. High CA repeat numbers in intron 13 of the endothelial nitric oxide synthase gene and increased risk of coronary artery disease. Pharmacogenetics. 2000 ; 10 (2). 133-140
17. Gelb BD. Marfan's syndrome and related disorders - more tightly connected than we thought. N Engl J Med. 2006 ; 355 (8). 841-844
18. Judge DP, Dietz HC. Marfan's syndrome. Lancet. 2005 ; 366 (9501). 1965-1976
19. Jordan CD, Bohling SD, Charbonneau NL, Sakai LY. Fibrillins in adult human ovary and polycystic ovary syndrome: is fibrillin-3 affected in PCOS?. J Histochem Cytochem. 2010 ; 58 (10). 903-915
20. Massague J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol. 2000 ; 1 (3). 169-178
21. Govinden R, Bhoola KD. Genealogy, expression, and cellular function of transforming growth factor-beta. Pharmacol Ther. 2003 ; 98 (2). 257-265
22. Letterio JJ, Roberts AB. Regulation of immune responses by TGF-beta. Annu Rev Immunol. 1998 ; 16: 137-161
23. Saharinen J, Hyytiainen M, Taipale J, Keski-Oja J. Latent transforming growth factor-beta binding proteins (LTBPs) - structural extracellular matrix proteins for targeting TGF-beta action. Cytokine Growth Factor Rev. 1999 ; 10 (2). 99-117
24. Welt CK, Taylor AE, Fox J, Messerlian GM, Adams JM, Schneyer AL. Follicular arrest in polycystic ovary syndrome is associated with deficient inhibin A and B biosynthesis. J Clin Endocrinol Metab. 2005 ; 90 (10). 5582-5587
25. Fleming R, Harborne L, MacLaughlin DT, et al. Metformin reduces serum mullerian-inhibiting substance levels in women with polycystic ovary syndrome after protracted treatment. Fertil Steril. 2005 ; 83 (1). 130-136
26. Eldar-Geva T, Spitz IM, Groome NP, Margalioth EJ, Homburg R. Follistatin and activin A serum concentrations in obese and non-obese patients with polycystic ovary syndrome. Hum Reprod. 2001 ; 16 (12). 2552-2556
27. Kevenaar ME, Laven JS, Fong SL, et al. A functional anti-mullerian hormone gene polymorphism is associated with follicle number and androgen levels in polycystic ovary syndrome patients. J Clin Endocrinol Metab. 2008 ; 93 (4). 1310-1316
28. Glister C, Richards SL, Knight PG. Bone morphogenetic proteins (BMP) -4, -6, and -7 potently suppress basal and luteinizing hormone-induced androgen production by bovine theca interna cells in primary culture: could ovarian hyperandrogenic dysfunction be caused by a defect in thecal BMP signaling?. Endocrinology. 2005 ; 146 (4). 1883-1892
29. Ingman WV, Robker RL, Woittiez K, Robertson SA. Null mutation in transforming growth factor beta1 disrupts ovarian function and causes oocyte incompetence and early embryo arrest. Endocrinology. 2006 ; 147 (2). 835-845
30. Urbanek M, Wu X, Vickery KR, et al. Allelic variants of the follistatin gene in polycystic ovary syndrome. J Clin Endocrinol Metab. 2000 ; 85 (12). 4455-4461
31. Hughesdon PE. Morphology and morphogenesis of the Stein-Leventhal ovary and of so-called "hyperthecosis". Obstet Gynecol Surv. 1982 ; 37 (2). 59-77
32. Urbanek M. The genetics of the polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab. 2007 ; 3 (2). 103-111
33. Urbanek M, Sam S, Legro RS, Dunaif A. Identification of a polycystic ovary syndrome susceptibility variant in fibrillin-3 and association with a metabolic phenotype. J Clin Endocrinol Metab. 2007 ; 92 (11). 4191-4198
34. Yalamanchi SK, Sam S, Cardenas MO, Holaday LW, Urbanek M, Dunaif A. Association of fibrillin-3 and transcription factor-7-like 2 gene variants with metabolic phenotypes in PCOS. Obesity (Silver Spring). 2012 ; 20 (6). 1273-1278
35. Norman RJ, Milner CR, Groome NP, Robertson DM. Circulating follistatin concentrations are higher and activin concentrations are lower in polycystic ovarian syndrome. Hum Reprod. 2001 ; 16 (4). 668-672
36. Villuendas G, Escobar-Morreale HF, Tosi F, Sancho J, Moghetti P, San Millan JL. Association between the D19S884 marker at the insulin receptor gene locus and polycystic ovary syndrome. Fertil Steril. 2003 ; 79 (1). 219-220
37. Tucci S, Futterweit W, Concepcion ES, et al. Evidence for association of polycystic ovary syndrome in caucasian women with a marker at the insulin receptor gene locus. J Clin Endocrinol Metab. 2001 ; 86 (1). 446-449
38. Prodoehl MJ, Hatzirodos N, Irving-Rodgers HF, et al. Genetic and gene expression analyses of the polycystic ovary syndrome candidate gene fibrillin-3 and other fibrillin family members in human ovaries. Mol Hum Reprod. 2009 ; 15 (12). 829-841
39. Huang X, Vaag A, Carlsson E, Hansson M, Ahren B, Groop L. Impaired cathepsin L gene expression in skeletal muscle is associated with type 2 diabetes. Diabetes. 2003 ; 52 (9). 2411-2418
40. Liao WX, Roy AC, Ng SC. Preliminary investigation of follistatin gene mutations in women with polycystic ovary syndrome. Mol Hum Reprod. 2000 ; 6 (7). 587-590
41. Jones MR, Wilson SG, Mullin BH, Mead R, Watts GF, Stuckey BG. Polymorphism of the follistatin gene in polycystic ovary syndrome. Mol Hum Reprod. 2007 ; 13 (4). 237-241
42. Sproul K, Jones MR, Mathur R, Azziz R, Goodarzi MO. Association study of four key folliculogenesis genes in polycystic ovary syndrome. BJOG. 2010 ; 117 (6). 756-760
43. Kevenaar ME, Themmen AP, van Kerkwijk AJ, et al. Variants in the ACVR1 gene are associated with AMH levels in women with polycystic ovary syndrome. Hum Reprod. 2009 ; 24 (1). 241-249
44. Chen ZJ, Zhao H, He L, et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet. 2011 ; 43 (1). 55-59
45. Prodoehl MJ, Irving-Rodgers HF, Bonner WM, et al. Fibrillins and latent TGFbeta binding proteins in bovine ovaries of offspring following high or low protein diets during pregnancy of dams. Mol Cell Endocrinol. 2009 ; 307 (1-2). 133-141
46. Hatzirodos N, Bayne RA, Irving-Rodgers HF, et al. Linkage of regulators of TGF-beta activity in the fetal ovary to polycystic ovary syndrome. FASEB J. 2011 ; 25 (7). 2256-2265
47. Ramirez F, Pereira L. The fibrillins. Int J Biochem Cell Biol. 1999 ; 31 (2). 255-259
48. Kielty CM, Sherratt MJ, Shuttleworth CA. Elastic fibres. J Cell Sci. 2002 ; 115 (pt 14). 2817-2828
49. Todorovic V, Rifkin DB. LTBPs, more than just an escort service. J Cell Biochem. 2012 ; 113 (2). 410-418
50. Ono RN, Sengle G, Charbonneau NL, et al. Latent transforming growth factor beta-binding proteins and fibulins compete for fibrillin-1 and exhibit exquisite specificities in binding sites. J Biol Chem. 2009 ; 284 (25). 16872-16881
51. LeClair R, Lindner V. The role of collagen triple helix repeat containing 1 in injured arteries, collagen expression, and transforming growth factor beta signaling. Trends Cardiovasc Med. 2007 ; 17 (6). 202-205
52. Christner PJ, Ayitey S.. Extracellular matrix containing mutated fibrillin-1 (Fbn1) down regulates Col1a1, Col1a2, Col3a1, Col5a1, and Col5a2 mRNA levels in Tsk/+ and Tsk/Tsk embryonic fibroblasts. Amino Acids. 2006 ; 30 (4). 445-451
53. Verrecchia F, Mauviel A. TGF-beta and TNF-alpha: antagonistic cytokines controlling type I collagen gene expression. Cell Signal. 2004 ; 16 (8). 873-880
54. Khan R, Sheppard R. Fibrosis in heart disease: understanding the role of transforming growth factor-beta in cardiomyopathy, valvular disease and arrhythmia. Immunology. 2006 ; 118 (1). 10-24
55. Chapman HA. Disorders of lung matrix remodeling. J Clin Invest. 2004 ; 113 (2). 148-157
56. Hetzel M, Bachem M, Anders D, Trischler G, Faehling M. Different effects of growth factors on proliferation and matrix production of normal and fibrotic human lung fibroblasts. Lung. 2005 ; 183 (4). 225-237
57. Kisseleva T, Brenner DA. Role of hepatic stellate cells in fibrogenesis and the reversal of fibrosis. J Gastroenterol Hepatol. 2007 ; 22 (suppl 1). S73 - S78
58. Prud'homme GJ. Pathobiology of transforming growth factor beta in cancer, fibrosis and immunologic disease, and therapeutic considerations. Lab Invest. 2007 ; 87 (11). 1077-1091
59. Bottinger EP. TGF-beta in renal injury and disease. Semin Nephrol. 2007 ; 27 (3). 309-320
60. Stein IF, Leventhal ML. Amenorhea associated with bilateral polcystic ovaries. American Journal of Obstetrics and Gynaecology. 1935 ; 29: 181-191
61. Nelson VL, Legro RS, Strauss JF, McAllister JM. Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol. 1999 ; 13 (6). 946-957
62. Nelson VL, Qin KN, Rosenfield RL, et al. The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2001 ; 86 (12). 5925-5933
63. Veiga-Lopez A, Ye W, Phillips DJ, Herkimer C, Knight PG, Padmanabhan V. Developmental programming: deficits in reproductive hormone dynamics and ovulatory outcomes in prenatal, testosterone-treated sheep. Biol Reprod. 2008 ; 78 (4). 636-647
64. Abbott DH, Barnett DK, Bruns CM, Dumesic DA. Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome?. Hum Reprod Update. 2005 ; 11 (4). 357-374
65. Webber LJ, Stubbs S, Stark J, et al. Formation and early development of follicles in the polycystic ovary. Lancet. 2003 ; 362 (9389). 1017-1021
66. Forsdike RA, Hardy K, Bull L, et al. Disordered follicle development in ovaries of prenatally androgenized ewes. J Endocrinol. 2007 ; 192 (2). 421-428
67. Hague WM, Adams J, Rodda C, et al. The prevalence of polycystic ovaries in patients with congenital adrenal hyperplasia and their close relatives. Clin Endocrinol (Oxf). 1990 ; 33 (4). 501-510
68. Barnes RB, Rosenfield RL, Ehrmann DA, et al. Ovarian hyperandrogynism as a result of congenital adrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women. J Clin Endocrinol Metab. 1994 ; 79 (5). 1328-1333
69. Davies MJ, March WA, Willson KJ, Giles LC, Moore VM. Birthweight and thinness at birth independently predict symptoms of polycystic ovary syndrome in adulthood. Hum Reprod. 2012 ; 27 (5). 1475-1480
70. Xu N, Kwon S, Abbott DH, et al. Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS)-like phenotypes in prenatally androgenized rhesus monkeys. PLoS One. 2011 ; 6 (11). e27286
71. Sabatier L, Miosge N, Hubmacher D, Lin G, Davis EC, Reinhardt DP. Fibrillin-3 expression in human development. Matrix Biol. 2011 ; 30 (1). 43-52
72. Trombly DJ, Woodruff TK, Mayo KE. Roles for transforming growth factor beta superfamily proteins in early folliculogenesis. Semin Reprod Med. 2009 ; 27 (1). 14-23
73. Raja-Khan N, Kunselman AR, Demers LM, Ewens KG, Spielman RS, Legro RS. A variant in the fibrillin-3 gene is associated with TGF-beta and inhibin B levels in women with polycystic ovary syndrome. Fertil Steril. 2010 ; 94 (7). 2916-2919
74. Kaur S, Archer KJ, Devi MG, Kriplani A, Strauss JF, Singh R. Differential gene expression in granulosa cells from polycystic ovary syndrome patients with and without insulin resistance: identification of susceptibility gene sets through network analysis. J Clin Endocrinol Metab. 2012 ; 97 (10). E2016 - E2021
75. Balen AH, Laven JS, Tan SL, Dewailly D. Ultrasound assessment of the polycystic ovary: international consensus definitions. Hum Reprod Update. 2003 ; 9 (6). 505-514
76. Legro RS, Chiu P, Kunselman AR, Bentley CM, Dodson WC, Dunaif A. Polycystic ovaries are common in women with hyperandrogenic chronic anovulation but do not predict metabolic or reproductive phenotype. J Clin Endocrinol Metab. 2005 ; 90 (5). 2571-2579
77. Woodruff TK, Shea LD. A new hypothesis regarding ovarian follicle development: ovarian rigidity as a regulator of selection and health. J Assist Reprod Genet. 2011 ; 28 (1). 3-6
78. Farquhar C, Lilford RJ, Marjoribanks J, Vandekerckhove P.. Laparoscopic "drilling" by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2005 ; (3). CD001122
79. Balen AH, Jacobs HS. A prospective study comparing unilateral and bilateral laparoscopic ovarian diathermy in women with the polycystic ovary syndrome [see comments]. Fertil Steril. 1994 ; 62 (5). 921-925
80. Zhu W, Fu Z, Chen X, et al. Transvaginal ultrasound-guided ovarian interstitial laser treatment in anovulatory women with polycystic ovary syndrome: a randomized clinical trial on the effect of laser dose used on the outcome. Fertil Steril. 2010 ; 94 (1). 268-275
81. Donesky BW, Adashi EY. Surgically induced ovulation in the polycystic ovary syndrome: wedge resection revisited in the age of laparoscopy. Fertil Steril. 1995 ; 63 (3). 439-463
82. Elting MW, Korsen TJ, Rekers-Mombarg LT, Schoemaker J. Women with polycystic ovary syndrome gain regular menstrual cycles when ageing. Hum Reprod. 2000 ; 15 (1). 24-28
83. Elting MW, Kwee J, Korsen TJ, Rekers-Mombarg LT, Schoemaker J. Aging women with polycystic ovary syndrome who achieve regular menstrual cycles have a smaller follicle cohort than those who continue to have irregular cycles. Fertil Steril. 2003 ; 79 (5). 1154-1160
84. Alsamarai S, Adams JM, Murphy MK, et al. Criteria for polycystic ovarian morphology in polycystic ovary syndrome as a function of age. J Clin Endocrinol Metab. 2009 ; 94 (12). 4961-4970
85. Armar NA, McGarrigle HH, Honour J, Holownia P, Jacobs HS, Lachelin GC.. Laparoscopic ovarian diathermy in the management of anovulatory infertility in women with polycystic ovaries: endocrine changes and clinical outcome. Fertil Steril. 1990 ; 53 (1). 45-49
86. Chang RJ, Laufer LR, Meldrum DR, et al. Steroid secretion in polycystic ovarian disease after ovarian suppression by a long-acting gonadotropin- releasing hormone agonist. J Clin Endocrinol Metab. 1983 ; 56 (5). 897-903
87. Lemieux S, Lewis GF, Ben-Chetrit A, Steiner G, Greenblatt EM. Correction of hyperandrogenemia by laparoscopic ovarian cautery in women with polycystic ovarian syndrome is not accompanied by improved insulin sensitivity or lipid-lipoprotein levels. J Clin Endocrinol Metab. 1999 ; 84 (11). 4278-4282
88. Azziz R, Ehrmann D, Legro RS, et al. Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial. J Clin Endocrinol Metab. 2001 ; 86 (4). 1626-1632
89. Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH.. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2010 ; (1). CD003053
90. Miao ZL, Guo L, Wang YX, et al. The intervention effect of Rosiglitozone in ovarian fibrosis of PCOS rats. Biomed Environ Sci. 2012 ; 25 (1). 46-52
91. West ER, Xu M, Woodruff TK, Shea LD. Physical properties of alginate hydrogels and their effects on in vitro follicle development. Biomaterials. 2007 ; 28 (30). 4439-4448
92. Xu M, West E, Shea LD, Woodruff TK. Identification of a stage-specific permissive in vitro culture environment for follicle growth and oocyte development. Biol Reprod. 2006 ; 75 (6). 916-923
93. Baranova A, Tran TP, Birerdinc A, Younossi ZM. Systematic review: association of polycystic ovary syndrome with metabolic syndrome and non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2011 ; 33 (7). 801-814
94. Fernandez IE, Eickelberg O. The impact of TGF-beta on lung fibrosis: from targeting to biomarkers. Proc Am Thorac Soc. 2012 ; 9 (3). 111-116
95. Antoniu SA, Kolb MR. Intedanib, a triple kinase inhibitor of VEGFR, FGFR and PDGFR for the treatment of cancer and idiopathic pulmonary fibrosis. IDrugs. 2010 ; 13 (5). 332-345
96. Daniels CE, Lasky JA, Limper AH, Mieras K, Gabor E, Schroeder DR. Imatinib treatment for idiopathic pulmonary fibrosis: randomized placebo-controlled trial results. Am J Respir Crit Care Med. 2010 ; 181 (6). 604-610
97. Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011 ; 365 (12). 1079-1087
98. Corson GM, Charbonneau NL, Keene DR, Sakai LY. Differential expression of fibrillin-3 adds to microfibril variety in human and avian, but not rodent, connective tissues. Genomics. 2004 ; 83 (3). 461-472
99. Dietz HC, Loeys B, Carta L, Ramirez F. Recent progress towards a molecular understanding of Marfan syndrome. Am J Med Genet C Semin Med Genet. 2005 ; 139C (1). 4-9
100. Neptune ER, Frischmeyer PA, Arking DE, et al. Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet. 2003 ; 33 (3). 407-411
101. Jones KB, Myers L, Judge DP, Kirby PA, Dietz HC, Sponseller PD. Toward an understanding of dural ectasia: a light microscopy study in a murine model of Marfan syndrome. Spine (Phila Pa 1976). 2005 ; 30 (3). 291-293
102. Ng CM, Cheng A, Myers LA, et al. TGF-beta-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome. J Clin Invest. 2004 ; 114 (11). 1586-1592
103. Habashi JP, Judge DP, Holm TM, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006 ; 312 (5770). 117-121
104. Coucke PJ, Willaert A, Wessels MW, et al. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. 2006 ; 38 (4). 452-457
105. Bobik A. Transforming growth factor-betas and vascular disorders. Arterioscler Thromb Vasc Biol. 2006 ; 26 (8). 1712-1720
106. Suthanthiran M, Li B, Song JO, et al. Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: a novel mediator of hypertension and/or target organ damage. Proc Natl Acad Sci U S A. 2000 ; 97 (7). 3479-3484
107. Rocha R, Stier CT. Pathophysiological effects of aldosterone in cardiovascular tissues. Trends Endocrinol Metab. 2001 ; 12 (7). 308-314
108. Williams JS. Williams GH. 50th anniversary of aldosterone. J Clin Endocrinol Metab. 2003 ; 88 (6). 2364-2372
109. Cascella T, Palomba S, Tauchmanova L, et al. Serum aldosterone concentration and cardiovascular risk in women with polycystic ovarian syndrome. J Clin Endocrinol Metab. 2006 ; 91 (11). 4395-4400
110. Stetler-Stevenson WG, Aznavoorian S, Liotta LA. Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol. 1993 ; 9: 541-573
111. Barcellos-Hoff MH, Dix TA. Redox-mediated activation of latent transforming growth factor-beta 1. Mol Endocrinol. 1996 ; 10 (9). 1077-1083
112. Wipff PJ, Hinz B. Integrins and the activation of latent transforming growth factor beta1 - an intimate relationship. Eur J Cell Biol. 2008 ; 87 (8-9). 601-615
113. Yu Q, Stamenkovic I. Cell surface-localized matrix metall-oproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev. 2000 ; 14 (2). 163-176
114. Taipale J, Miyazono K, Heldin CH, Keski-Oja J. Latent transforming growth factor-beta 1 associates to fibroblast extracellular matrix via latent TGF-beta binding protein. J Cell Biol. 1994 ; 124 (1-2). 171-181