Fibroblast autophagy in fibrotic disorders

Journal of Pathology

Volumn 229, Issue 2, 2013, Pages 208-220

  Principe, Domenico Del ^a   Lista, Pasquale ^b   Malorni, Walter ^a,b   Giammarioli, Anna Maria ^b  

^a San Raffaele Institute Sulmona   (Italy)

^b ISTITUTO SUPERIORE DI SANITÀ   (Italy)

Author keywords

autophagy; cytokines; fibroblasts; fibrotic disorders; immune system

Indexed keywords

5' AMP ACTIVATED PROTEIN KINASE; ACYLTRANSFERASE; INTERLEUKIN 13; INTERLEUKIN 17; INTERLEUKIN 4; MAMMALIAN TARGET OF RAPAMYCIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PROTEIN P53; SMAD2 PROTEIN; SMAD3 PROTEIN; SMAD4 PROTEIN; UNCLASSIFIED DRUG;

AUTOPHAGY; CELL DIFFERENTIATION; CELL SURVIVAL; COLLAGEN DEGRADATION; DEACETYLATION; DISEASE COURSE; ENDOPLASMIC RETICULUM; ENZYME ACTIVITY; FIBROBLAST; FIBROGENESIS; FIBROSING ALVEOLITIS; FIBROSIS; HEART MUSCLE FIBROSIS; HUMAN; HYPERTROPHIC SCAR; IMMUNE RESPONSE; IMMUNE SYSTEM; KIDNEY FIBROSIS; LIVER FIBROSIS; LYSOSOME; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION;

EID: 84871037851     PISSN: 00223417     EISSN: 10969896     Source Type: Journal    
DOI: 10.1002/path.4115     Document Type: Review

References (176)

1. Kisseleva T, Brenner DA,. Mechanisms of fibrogenesis. Exp Biol Med (Maywood) 2008; 233: 109-122. (Pubitemid 351231543)
2. Wynn TA,. Cellular and molecular mechanisms of fibrosis. J Pathol 2008; 214: 199-210. (Pubitemid 351160157)
3. Jacob M, Chang L, Puré E,. Fibroblast activation protein in remodeling tissues. Curr Mol Med 2012; [Epub ahead of print].
4. Lu P, Takai K, Weaver VM, et al,. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol 2011; 3 (12): ii, a005058; doi: 10.1101/cshperspect.a005058.
5. Vargová V, Pytliak M, Mechírová V. Matrix metalloproteinases. EXS 2012; 103: 1-33.
6. Clark IM, Swingler TE, Sampieri CL, et al,. The regulation of matrix metalloproteinases and their inhibitors. Int J Biochem Cell Biol 2008; 40: 1362-1378.
7. Amǎlinei C, Cǎruntu ID, Giuşcǎ SE, et al,. Matrix metalloproteinases involvement in pathologic conditions. Rom J Morphol Embryol 2010; 51: 215-228.
8. Raghow R,. The role of extracellular matrix in post-inflammatory wound healing and fibrosis. FASEB J 1994; 8: 823-831. (Pubitemid 24268873)
9. Mast BA, Schultz GS,. Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Repair Regen 1996; 4: 411-420. (Pubitemid 126670858)
10. Mutsaers SE, Bishop JE, McGrouther G, et al,. Mechanisms of tissue repair: from wound healing to fibrosis. Int J Biochem Cell Biol 1997; 29: 5-17. (Pubitemid 27096415)
11. Chan MW, Hinz B, McCulloch CA,. Mechanical induction of gene expression in connective tissue cells. Methods Cell Biol 2010; 98: 178-205.
12. Benjamin MM, Khalil RA,. Matrix metalloproteinase inhibitors as investigative tools in the pathogenesis and management of vascular disease. EXS 2012; 103: 209-279.
13. Friedman SL,. Mechanisms of disease: mechanisms of hepatic fibrosis and therapeutic implications. Nat Clin Pract Gastroenterol Hepatol 2004; 1: 98-105. (Pubitemid 40823677)
14. Clancy RM, Buyon JP,. Autoimmune-associated congenital heart block: dissecting the cascade from immunologic insult to relentless fibrosis. Anat Rec A Discov Mol Cell Evol Biol 2004; 280: 1027-1035. (Pubitemid 39319328)
15. Liu S, Taghavi R, Leask A,. Connective tissue growth factor is induced in bleomycin-induced skin scleroderma. J Cell Commun Signal 2010; 4: 25-30.
16. Keeley EC, Mehrad B, Strieter RM,. The role of fibrocytes in fibrotic diseases of the lungs and heart. Fibrogen Tissue Repair 2011; 4: 2.
17. Kolonin MG, Evans KW, Mani SA, et al,. Alternative origins of stroma in normal organs and disease. Stem Cell Res 2012; 8: 312-323.
18. Wick G, Backovic A, Rabensteiner E, et al,. The immunology of fibrosis: innate and adaptive responses. Trends Immunol 2010; 31: 110-109.
19. Leask A, Abraham DJ,. TGFβ signaling and the fibrotic response. FASEB J 2004; 18: 816-827.
20. Meneghin A, Hogaboam CM,. Infectious disease, the innate immune response, and fibrosis. J Clin Invest 2007; 117: 530-538. (Pubitemid 46348507)
21. Barron L, Wynn TA,. Fibrosis is regulated by Th2 and Th17 responses and by dynamic interactions between fibroblasts and macrophages. Am J Physiol Gastrointest Liver Physiol 2011; 300: G723-728.
22. Mahdavian Delavary B, van der Veer WM, et al,. Macrophages in skin injury and repair. Immunobiology 2011; 216: 753-762.
23. Kajihara I, Jinnin M, Honda N, et al,. Scleroderma dermal fibroblasts overexpress vascular endothelial growth factor due to autocrine transforming growth factor-β signaling. Mod Rheumatol 2012. [Epub ahead of print]
24. Nakerakanti S, Trojanowska M,. The role of TGFβ receptors in fibrosis. Open Rheumatol J 2012; 6: 156-162.
25. Kim SI, Na HJ, Ding Y, et al,. Autophagy promotes intracellular degradation of type I collagen induced by transforming growth factor (TGF)-β1. J Biol Chem 2012; 287: 11677-11688.
26. Barrientos S, Stojadinovic O, Golinko MS, et al,. Growth factors and cytokines in wound healing. Wound Repair Regen 2008; 16: 585-601.
27. Galluzzi L, Vanden Berghe T, Vanlangenakker N, et al. Programmed necrosis from molecules to health and disease. Int Rev Cell Mol Biol 2011; 289: 1-35.
28. Gilmore AP,. Anoikis. Cell Death Differ 2005; 12: 1473-1477. (Pubitemid 41553981)
29. Overholtzer M, Mailleux AA, Mouneimne G, et al,. A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion. Cell 2007; 131: 966-979. (Pubitemid 350138090)
30. Yuan J, Kroemer G,. Alternative cell death mechanisms in development and beyond. Genes Dev 2010; 24: 2592-2602.
31. Klionsky DJ,. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 2007; 8: 931-937. (Pubitemid 47622558)
32. Kroemer G, Mariño G, Levine B,. Autophagy and the integrated stress response. Mol Cell 2010; 40: 280-293.
33. Nishiyama J, Matsuda K, Kakegawa W, et al,. Reevaluation of neurodegeneration in lurcher mice: constitutive ion fluxes cause cell death with, not by, autophagy. J Neurosci 2010; 30: 2177-2187.
34. Berry DL, Baehrecke EH,. Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell 2007; 131: 1137-1148. (Pubitemid 350235023)
35. McPhee CK, Baehrecke EH,. The engulfment receptor Draper is required for autophagy during cell death. Autophagy 2010; 6: 1192-1193.
36. McPhee CK, Balgley BM, Nelson C, et al,. Identification of factors that function in Drosophila salivary gland cell death during development using proteomics. Cell Death Differ 2012; doi: 10.1038/cdd.2012.110. [Epub ahead of print]
37. Levine B, Yuan J,. Autophagy in cell death: an innocent convict? J Clin Invest 2005; 115: 2679-2688. (Pubitemid 41434392)
38. Grishchuk Y, Ginet V, Truttmann AC, et al,. Beclin 1-independent autophagy contributes to apoptosis in cortical neurons. Autophagy 2011; 7: 1115-1131.
39. Edinger AL, Thompson CB,. Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol 2004; 16: 663-669. (Pubitemid 39463117)
40. Maiuri MC, Zalckvar E, Kimchi A, et al,. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 2007; 8: 741-752. (Pubitemid 47312826)
41. Levine B, Sinha S, Kroemer G,. Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 2008; 4: 600-606.
42. Gordy C, He YW,. The crosstalk between autophagy and apoptosis: where does this lead? Protein Cell 2012; 3: 17-27.
43. Buckley CD, Pilling D, Lord JM, et al,. Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation. Trends Immunol 2001; 22: 199-204. (Pubitemid 32673659)
44. Xie Z, Klionsky DJ,. Autophagosome formation: core machinery and adaptations. Nat Cell Biol 2007; 9: 1102-1109. (Pubitemid 47500484)
45. Hamasaki M, Yoshimori T,. Where do they come from? Insights into autophagosome formation. FEBS Lett 2010; 584: 1296-1301.
46. Levine B, Mizushima N, Virgin HW,. Autophagy in immunity and inflammation. Nature 2011; 469: 323-335.
47. Choi AJ, Ryter SW,. Autophagy in inflammatory diseases. Int J Cell Biol 2011; Article No. 732798. doi: 10.1155/2011/732798
48. Levine B, Deretic V,. Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 2007; 7: 767-777. (Pubitemid 47480305)
49. Münz C,. Antigen processing via autophagy-not only for MHC class II presentation anymore? Curr Opin Immunol 2010; 22: 89-93.
50. Rubinsztein DC,. The roles of intracellular protein-degradation pathways in neurodegeneration. Nature 2006; 443: 780-786. (Pubitemid 44622682)
51. Bernales S, McDonald KL, Walter P,. Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLoS Biol 2006; 4: 423.
52. Kraft C, Deplazes A, Sohrmann M, et al,. Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Nat Cell Biol 2008; 10: 602-610. (Pubitemid 351627380)
53. Kim PK, Hailey DW, Mullen RT, et al., Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. Proc Natl Acad Sci USA 2008; 105: 20567-20574.
54. Green DR, Galluzzi L, Kroemer G,. Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science 2011; 333: 1109-1112.
55. Narendra DP, Youle RJ,. Targeting mitochondrial dysfunction: role for PINK1 and Parkin in mitochondrial quality control. Antioxid Redox Signal 2011; 14: 1929-1938.
56. Jin SM, Youle RJ,. PINK1- and Parkin-mediated mitophagy at a glance. J Cell Sci 2012; 125: 795-799.
57. Yao TP,. The role of ubiquitin in autophagy-dependent protein aggregate processing. Genes Cancer 2010; 1: 779-786.
58. Geisler S, Holmström KM, Skujat D, et al,. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 2010; 12: 119-131.
59. Johansen T, Lamark T,. Selective autophagy mediated by autophagic adapter proteins. Autophagy 2011; 7: 279-296.
60. Su H, Wang X,. p62 stages an interplay between the ubiquitin-proteasome system and autophagy in the heart of defense against proteotoxic stress. Trends Cardiovasc Med 2011; 21: 224-228.
61. Klionsky DJ, Abdalla FC, Abeliovich H, et al,. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 2012; 8: 1-100.
62. Axe EL, Walker SA, Manifava M, et al,. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol 2008; 182: 685-701.
63. Hayashi-Nishino M, Fujita N, Noda T, et al,. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat Cell Biol 2009; 11: 1433-1437.
64. Giammarioli AM, Gambardella L, Barbati C, et al,. Differential effects of the glycolysis inhibitor 2-deoxy- d -glucose on the activity of pro-apoptotic agents in metastatic melanoma cells, and induction of a cytoprotective autophagic response. Int J Cancer 2012; 131: E337-347.
65. Hailey DW, Rambold AS, Satpute-Krishnan P, et al,. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 2010; 141: 656-667.
66. Ravikumar B, Moreau K, Rubinsztein DC,. Plasma membrane helps autophagosomes grow. Autophagy 2010; 6: 1184-1186.
67. Yamamoto H, Kakuta S, Watanabe TM, et al,. Atg9 vesicles are an important membrane source during early steps of autophagosome formation. J Cell Biol 2012; 198: 219-233.
68. Martelli AM, Evangelisti C, Chiarini F, et al,. The emerging role of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling network in normal myelopoiesis and leukemogenesis. Biochim Biophys Acta 2010; 1803: 991-1002.
69. Feldman ME, Apsel B, Uotila A, et al,. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 andmTORC2. PLoS Biol 2009; 7: e38.
70. Hoyer-Hansen M, Jäättelä M,. Autophagy: an emerging target for cancer therapy. Autophagy 2008; 4: 574-580.
71. Fimia GM, Piacentini M,. Regulation of autophagy in mammals and its interplay with apoptosis. Cell Mol Life Sci 2010; 67: 1581-1588.
72. Liang C, Feng P, Ku B, et al,. Autophagic and tumor suppressor activity of a novel Beclin 1-binding protein, UVRAG. Nat Cell Biol 2006; 8: 688-699.
73. Fimia GM, Stoykova A, Romagnoli A, et al,. Ambra1 regulates autophagy and development of the nervous system. Nature 2007; 447: 1121-1125. (Pubitemid 47014434)
74. Sun Q, Fan W, Chen K, et al,. Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. Proc Natl Acad Sci USA 2008; 105: 19211-19216.
75. Matsunaga K, Saitoh T, Tabata K, et al,. Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol 2009; 11: 385-396.
76. Meijer AJ, Codogno P,. Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol 2004; 36: 2445-2462. (Pubitemid 39119758)
77. Maiuri MC, Tasdemir E, Criollo A, et al,. Control of autophagy by oncogenes and tumor suppressor genes. Cell Death Differ 2009; 16: 87-93.
78. Inoki K, Kim J, Guan KL,. AMPK and mTOR in cellular energy homeostasis and drug targets. Annu Rev Pharmacol Toxicol 2012; 52: 381-400.
79. Mao K, Klionsky DJ,. AMPK activates autophagy by phosphorylating ULK1. Circ Res 2011; 108: 787-788.
80. Mack HI, Zheng B, Asara J, et al,. AMPK-dependent phosphorylation of ULK1 regulates ATG9 localization. Autophagy 2012; 8: 1197-1214.
81. Cully M, You H, Levine AJ, et al,. Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 2006; 6: 184-192. (Pubitemid 43292562)
82. Nho RS, Xia H, Diebold D, et al,. PTEN regulates fibroblast elimination during collagen matrix contraction. J Biol Chem 2006; 281: 33291-33301. (Pubitemid 46036712)
83. Arico S, Petiot A, Bauvy C, et al,. The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway. J Biol Chem 2001; 276: 35243-35246.
84. Lee IH, Cao L, Mostoslavsky R, et al,. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA 2008; 105: 3374-3379. (Pubitemid 351723560)
85. Wang J, Kim TH, Ahn MY, et al,. Sirtinol, a class III HDAC inhibitor, induces apoptotic and autophagic cell death in MCF-7 human breast cancer cells. Int J Oncol 2012; 41: 1101-1109.
86. Lee IH, Finkel T,. Regulation of autophagy by the p300 acetyltransferase. J Biol Chem 2009; 284: 6322-6328.
87. Kume S, Uzu T, Horiike K, et al,. Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest 2010; 120: 1043-1055.
88. Vogelstein B, Lane D, Levine AJ,. Surfing the p53 network. Nature 2000; 408: 307-310.
89. Green DR, Kroemer G,. Cytoplasmic functions of the tumour suppressor p53. Nature 2009; 458: 1127-1130.
90. Morselli E, Shen S, Ruckenstuhl C, et al,. p53 inhibits autophagy by interacting with the human ortholog of yeast Atg17, RB1CC1/FIP200. Cell Cycle 2011; 10: 2763-2769.
91. Galluzzi L, Morselli E, Kepp O, et al,. Defective autophagy control by the p53 rheostat in cancer. Cell Cycle 2010; 9: 250-255.
92. Stambolic V, MacPherson D, Sas D, et al,. Regulation of PTEN transcription by p53. Mol Cell 2001; 8: 317-325. (Pubitemid 32831549)
93. Tasdemir E, Maiuri MC, Galluzzi L, et al,. Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 2008; 10: 676-687. (Pubitemid 351772933)
94. Tallóczy Z, Jiang W, Virgin HW 4th, et al,. Regulation of starvation- and virus-induced autophagy by the eIF2α kinase signaling pathway. Proc Natl Acad Sci USA 2002; 99: 190-195. (Pubitemid 34060339)
95. Kadowaki M, Kanazawa T,. Amino acids as regulators of proteolysis. J Nutr 2003; 133: 2052-2056S.
96. Vidal RL, Hetz C,. Crosstalk between the UPR and autophagy pathway contributes to handling cellular stress in neurodegenerative disease. Autophagy 2012; 8: 970-972.
97. Duran JM, Anjard C, Stefan C, et al,. Unconventional secretion of Acb1 is mediated by autophagosomes. J Cell Biol 2010; 188: 527-536.
98. Bruns C, McCaffery JM, Curwin AJ, et al,. Biogenesis of a novel compartment for autophagosome-mediated unconventional protein secretion. J Cell Biol 2011; 195: 979-992.
99. Deretic V, Jiang S, Dupont N,. Autophagy intersections with conventional and unconventional secretion in tissue development, remodeling and inflammation. Trends Cell Biol 2012; 22: 397-406.
100. Qin L, Wang Z, Tao L, et al,. ER stress negatively regulates AKT/TSC/mTOR pathway to enhance autophagy. Autophagy 2010; 6: 239-247.
101. Chen JJ, Jin PS, Zhao S, et al,. Effect of heat shock protein 47 on collagen synthesis of keloid in vivo. ANZ J Surg 2011; 81: 425-430.
102. Appenzeller-Herzog C, Hall MN,. Bidirectional crosstalk between endoplasmic reticulum stress and mTOR signaling. Trends Cell Biol 2012; 22: 274-282.
103. Ishida Y, Nagata K,. Autophagy eliminates a specific species of misfolded procollagen and plays a protective role in cell survival against ER stress. Autophagy 2009; 5: 1217-1219.
104. Ding WX, Yin XM,. Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome. Autophagy 2008; 4: 141-150.
105. Nijholt DA, De Kimpe L, Elfrink HL, et al,. Removing protein aggregates: the role of proteolysis in neurodegeneration. Curr Med Chem 2011; 18: 2459-2476.
106. Ishida Y, Nagata K,. Hsp47 as a collagen-specific molecular chaperone. Methods Enzymol 2011; 499: 167-182.
107. Tannous P, Zhu H, Johnstone JL, et al,. Autophagy is an adaptive response in desmin-related cardiomyopathy. Proc Natl Acad Sci USA 2008; 105: 9745-9750. (Pubitemid 352031371)
108. Georgescu SP, Aronovitz MJ, Iovanna JL, et al,. Decreased metalloprotease 9 induction, cardiac fibrosis, and higher autophagy after pressure overload in mice lacking the transcriptional regulator p8. Am J Physiol Cell Physiol 2011; 301: C1046-1056.
109. Aránguiz-Urroz P, Canales J, Copaja M, et al,. β2-adrenergic receptor regulates cardiac fibroblast autophagy and collagen degradation. Biochim Biophys Acta 2011; 1812: 23-31.
110. Patel AS, Lin L, Geyer A, et al,. Autophagy in idiopathic pulmonary fibrosis. PLoS One 2012; 7: e41394.
111. Yang HZ, Wang JP, Mi S, et al,. TLR4 activity is required in the resolution of pulmonary inflammation and fibrosis after acute and chronic lung injury. Am J Pathol 2012; 180: 275-292.
112. Shi JH, Hu DH, Zhang ZF, et al,. Reduced expression of microtubule-associated protein 1 light chain 3 in hypertrophic scars. Arch Dermatol Res 2012; 304: 209-215.
113. Malorni W, Matarrese P, Tinari A, et al,. Xeno-cannibalism: a survival 'escamotage'. Autophagy 2007; 3: 75-77.
114. Tinari A, Matarrese P, Minetti M, et al,. Hyperphagia by self- and xeno-cannibalism: cell death by indigestion? A reminiscence of the Phedrus Fabula 'Rana Rupta et Bos'? Autophagy 2008; 4: 128-130.
115. Matarrese P, Ciarlo L, Tinari A, et al,. Xeno-cannibalism as an exacerbation of self-cannibalism: a possible fruitful survival strategy for cancer cells. Curr Pharm Des 2008; 14: 245-252. (Pubitemid 351516869)
116. Lugini L, Matarrese P, Tinari A, et al,. Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells. Cancer Res 2006; 66: 3629-3638.
117. Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, et al,. The autophagic tumor stroma model of cancer or 'battery-operated tumor growth': a simple solution to the autophagy paradox. Cell Cycle 2010; 9: 4297-4306.
118. Castello-Cros R, Bonuccelli G, Molchansky A, et al,. Matrix remodeling stimulates stromal autophagy, 'fueling' cancer cell mitochondrial metabolism and metastasis. Cell Cycle 2011; 10: 2021-2034.
119. Cho HJ, Jung JI, Lim DY, et al,. Bone marrow-derived, alternatively activated macrophages enhance solid tumor growth and lung metastasis of mammary carcinoma cells in a Balb/C mouse orthotopic model. Breast Cancer Res 2012; 14: R81.
120. Hernández-Gea V, Friedman SL,. Autophagy fuels tissue fibrogenesis. Autophagy 2012; 8: 849-850.
121. Hernández-Gea V, Ghiassi-Nejad Z, Rozenfeld R, et al,. Autophagy releases lipid that promotes fibrogenesis by activated hepatic stellate cells in mice and in human tissues. Gastroenterology 2012; 142: 938-946.
122. Singh R, Cuervo AM,. Lipophagy: connecting autophagy and lipid metabolism. Int J Cell Biol 2012; [Epub ahead of print 2012 Mar 28]
123. Abeles AM, Pillinger MH,. The role of the synovial fibroblast in rheumatoid arthritis: cartilage destruction and the regulation of matrix metalloproteinases. Bull NYU Hosp Joint Dis 2006; 64: 20-24. (Pubitemid 44625529)
124. Shin YJ, Han SH, Kim DS, et al,. Autophagy induction and CHOP under-expression promotes survival of fibroblasts from rheumatoid arthritis patients under endoplasmic reticulum stress. Arthritis Res Ther 2010; 12: R19.
125. Haringman JJ, Gerlag DM, Zwinderman AH, et al,. Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis. Ann Rheum Dis 2005; 64: 834-838. (Pubitemid 40733904)
126. Kennedy A, Fearon U, Veale DJ, et al,. Macrophages in synovial inflammation. Front Immunol 2011; 2: 1-9.
127. Sica A, Mantovani A,. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 2012; 122: 787-795.
128. Nimmerjahn F, Milosevic S, Behrends U, et al,. Major histocompatibility complex class II-restricted presentation of a cytosolic antigen by autophagy. Eur J Immunol 2003; 33: 1250-1259. (Pubitemid 36609143)
129. Delgado M, Singh S, De Haro S, et al,. Autophagy and pattern recognition receptors in innate immunity. Immunol Rev 2009; 227: 189-202.
130. Del Principe D, Vona R, Giordani L, et al,. Defective autophagy in fibroblasts may contribute to fibrogenesis in autoimmune processes. Curr Pharm Des 2011; 17: 3878-3887.
131. Bouros D,. Interferon gamma for idiopathic pulmonary fibrosis. Lancet 2009; 374: 180-182.
132. King TE Jr,. Bosentan for idiopathic pulmonary fibrosis. Curr Opin Investig Drugs 2008; 9: 1171-1179.
133. Boin F, De Fanis U, Bartlett SJ, et al,. T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease. Arthritis Rheum 2008; 58: 1165-1174. (Pubitemid 351564020)
134. Chizzolini C, Brembilla NC, Montanari E, et al,. Fibrosis and immune dysregulation in sistemi sclerosis. Autoimmun Rev 2011; 10: 276-281.
135. Braga TT, Correa-Costa M, Guise YF, et al,. MyD88 signaling pathway is involved in renal fibrosis by favoring a Th2 immune response and activating alternative M2 macrophages. Mol Med 2012. [Epub ahead of print 2012 July 5 doi number: 10.2119/molmed.2012.00131]
136. Morishima Y, Ishii Y,. Targeting Th2 cytokines in fibrotic diseases. Curr Opin Investig Drugs 2010; 11: 1229-1238.
137. Ghadimi D, de Vrese M, Heller KJ, Schrezenmeir J,. Lactic acid bacteria enhance autophagic ability of mononuclear phagocytes by increasing Th1 autophagy-promoting cytokine (IFNγ) and nitric oxide (NO) levels and reducing Th2 autophagy-restraining cytokines (IL-4 and IL-13) in response to Mycobacterium tuberculosis antigen. Int Immunopharmacol 2010; 10: 694-706.
138. Mi S, Li Z, Yang HZ, et al,. Blocking IL-17A promotes the resolution of pulmonary inflammation and fibrosis via TGFβ1-dependent and -independent mechanisms. J Immunol 2011; 187: 3003-3014.
139. Mosser DM, Edwards JP,. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008; 8: 958-969 [review]; erratum in: Nat Rev Immunol 2010; 10: 460.
140. Mantovani A, Sica A, Sozzani S, et al,. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004; 25: 677-686. (Pubitemid 39457982)
141. Martinez FO, Helming L, Gordon S,. Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 2009; 27: 451-483 [review].
142. Fairweather D, Cihakova D,. Alternatively activated macrophages in infection and autoimmunity. J Autoimmun 2009; 33: 222-230.
143. Wynn TA, Barron L,. Macrophages: master regulators of inflammation and fibrosis. Semin Liver Dis 2010; 30: 245-257 [review].
144. Shi CS, Shenderov K, Huang NN, et al,. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol 2012; 13: 255-263.
145. Inohara N, Chamaillard M, McDonald C, et al,. NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. Annu Rev Biochem 2005; 74: 355-383. (Pubitemid 40995511)
146. Takeuchi O, Akira S,. MDA5/RIG-I and virus recognition. Curr Opin Immunol 2008; 20: 17-22.
147. Barton GM, Kagan JC,. A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nat Rev Immunol 2009; 9: 535-542.
148. Kumar H, Kawai T, Akira S,. Pathogen recognition by the innate immune system. Int Rev Immunol 2011; 30: 16-34.
149. Olive C,. Pattern recognition receptors: sentinels in innate immunity and targets of new vaccine adjuvants. Expert Rev Vaccines 2012; 11: 237-256.
150. van Riet E, Everts B, Retra K, et al,. Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: molecular correlates for Th1/Th2 polarization. BMC Immunol 2009; 10: 9.
151. + T cells. J Immunol 2009; 182: 3372-3379.
152. Suzuki HI, Kiyono K, Miyazono K,. Regulation of autophagy by transforming growth factor-β (TGFβ) signaling. Autophagy 2010; 6: 645-647.
153. Mead AL, Wong TT, Cordeiro MF, et al,. Evaluation of anti-TGFβ2 antibody as a new postoperative anti-scarring agent in glaucoma surgery. Invest Ophthalmol Vis Sci 2003; 44: 3394-3401. (Pubitemid 36909776)
154. Kiyono K, Suzuki HI, Matsuyama H, et al,. Autophagy is activated by TGFβ and potentiates TGFβ-mediated growth inhibition in human hepatocellular carcinoma cells. Cancer Res 2009; 69: 8844-8852.
155. Goc A, Choudhary M, Byzova TV, et al,. TGFβ- and bleomycin-induced extracellular matrix synthesis is mediated through Akt and mammalian target of rapamycin (mTOR). J Cell Physiol 2011; 226: 3004-3013.
156. White ES, Atrasz RG, Hu B, et al,. Negative regulation of myofibroblast differentiation by PTEN (phosphatase and tensin homolog deleted on chromosome 10). Am J Respir Crit Care Med 2006; 173: 112-121. (Pubitemid 43069796)
157. Xia H, Diebold D, Nho R, et al,. Pathological integrin signaling enhances proliferation of primary lung fibroblasts from patients with idiopathic pulmonary fibrosis. J Exp Med 2008; 205: 1659-1672. (Pubitemid 351962029)
158. Parapuram SK, Shi-wen X, Elliott C, et al,. Loss of PTEN expression by dermal fibroblasts causes skin fibrosis. J Invest Dermatol 2011; 131: 1996-2003.
159. Fried L, Kirsner RS, Bhandarkar S, et al,. Efficacy of rapamycin in scleroderma: a case study. Lymphat Res Biol 2008; 6: 217-219.
160. Yoshizaki A, Yanaba K, Yoshizaki A, et al,. Treatment with rapamycin prevents fibrosis in tight-skin and bleomycin-induced mouse models of systemic sclerosis. Arthritis Rheum 2010; 62: 2476-2487.
161. Su TI, Khanna D, Furst DE, et al,. Rapamycin versus methotrexate in early diffuse systemic sclerosis: results from a randomized, single-blind pilot study. Arthritis Rheum 2009; 60: 3821-3830.
162. Wei J, Ghosh AK, Sargent JL, et al,. PPARγ downregulation by TGFβ in fibroblast and impaired expression and function in systemic sclerosis: a novel mechanism for progressive fibrogenesis. PLoS One 2010; 5: e13778.
163. Samuel GH, Bujor AM, Nakerakanti SS, et al,. Autocrine transforming growth factor-β signaling regulates extracellular signal-regulated kinase 1/2 phosphorylation via modulation of protein phosphatase 2A expression in scleroderma fibroblasts. Fibrogen Tissue Repair 2010; 6: 3-25.
164. Kumarswamy R, Volkmann I, Jazbutyte V, et al,. Transforming growth factor-β-induced endothelial-to-mesenchymal transition is partly mediated by microRNA-21. Arterioscler Thromb Vasc Biol 2012; 32: 361-369.
165. Sha W, Thompson K, South J, et al,. Loss of PPARγ expression by fibroblasts enhances dermal wound closure. Fibrogen Tissue Repair 2012; 5: 5.
166. Hasegawa H, Takano H, Zou Y, et al,. Pioglitazone, a peroxisome proliferator-activated receptor-γ activator, ameliorates experimental autoimmune myocarditis by modulating Th1/Th2 balance. JMol Cell Cardiol 2005; 38: 257-265. (Pubitemid 40215195)
167. Trojanowska M,. Noncanonical transforming growth factor-β signaling in scleroderma fibrosis. Curr Opin Rheumatol 2009; 21: 623-629.
168. Ammanamanchi S, Brattain MG,. Restoration of transforming growth factor-β signaling through receptor RI induction by histone deacetylase activity inhibition in breast cancer cells. J Biol Chem 2004; 279: 32620-32625. (Pubitemid 39014719)
169. Lim JY, Oh MA, Kim WH, et al,. AMP-activated protein kinase inhibits TGFβ-induced fibrogenic responses of hepatic stellate cells by targeting transcriptional coactivator p300. J Cell Physiol 2012; 227: 1081-1089.
170. Bhattacharyya S, Ghosh AK, Pannu J, et al,. Fibroblast expression of the coactivator p300 governs the intensity of profibrotic response to transforming growth factor-β. Arthritis Rheum 2005; 52: 1248-1258. (Pubitemid 40530133)
171. Ghosh AK, Varga J,. The transcriptional coactivator and acetyltransferase p300 in fibroblast biology and fibrosis. J Cell Physiol 2007; 213: 663-671. (Pubitemid 350058260)
172. Lam AP, Flozak AS, Russell S, et al,. Nuclear β-catenin is increased in systemic sclerosis pulmonary fibrosis and promotes lung fibroblast migration and proliferation. Am J Respir Cell Mol Biol 2011; 45: 915-922.
173. Wei J, Bhattacharyya S, Tourtellotte WG, et al,. Fibrosis in systemic sclerosis: emerging concepts and implications for targeted therapy. Autoimmun Rev 2011; 10: 267-275.
174. Rombouts K, Niki T, Greenwel P, Vandermonde A, et al,. Trichostatin A, a histone deacetylase inhibitor, suppresses collagen synthesis and prevents TGFβ1-induced fibrogenesis in skin fibroblasts. Exp Cell Res 2002; 278: 184-197. (Pubitemid 35002103)
175. McEwan DG, Dikic I,. The Three Musketeers of autophagy: phosphorylation, ubiquitylation and acetylation. Trends Cell Biol 2011; 21: 195-201.
176. Pang M, Zhuang S,. Histone deacetylase: a potential therapeutic target for fibrotic disorders. J Pharmacol Exp Ther 2010; 335: 266-272.