Autophagy fosters myofibroblast differentiation through MTORC2 activation and downstream upregulation of CTGF

Autophagy

Volumn 10, Issue 12, 2014, Pages 2193-2207

  Bernard, Monique ^a   Dieudé, Mélanie ^a   Yang, Bing ^a   Hamelin, Katia ^a   Underwood, Katy ^a   Hébert, Marie Josée ^a  

^a UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

AKT; ATG7; Autophagy; Connective tissue growth factor (CTGF); Differentiation; Fibroblast; Fibrosis; MTORC2; Myofibroblast; Rapamycin

Indexed keywords

CONNECTIVE TISSUE GROWTH FACTOR; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; PHOSPHATIDYLINOSITOL 3 KINASE; TRANSFORMING GROWTH FACTOR BETA; CTGF PROTEIN, HUMAN; MULTIPROTEIN COMPLEX; TARGET OF RAPAMYCIN KINASE; TOR COMPLEX 2;

ARTICLE; AUTOPHAGY; CELL DIFFERENTIATION; DOWN REGULATION; ENZYME ACTIVATION; MYOFIBROBLAST; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; UPREGULATION; CELL CULTURE; CYTOLOGY; HUMAN; METABOLISM; PHYSIOLOGY; TRANSCRIPTION INITIATION;

AUTOPHAGY; CELL DIFFERENTIATION; CELLS, CULTURED; CLASS III PHOSPHATIDYLINOSITOL 3-KINASES; CONNECTIVE TISSUE GROWTH FACTOR; HUMANS; MULTIPROTEIN COMPLEXES; MYOFIBROBLASTS; PHOSPHATIDYLINOSITOL 3-KINASES; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; TRANSCRIPTIONAL ACTIVATION; TRANSFORMING GROWTH FACTOR BETA; UP-REGULATION;

EID: 84922354513     PISSN: 15548627     EISSN: 15548635     Source Type: Journal    
DOI: 10.4161/15548627.2014.981786     Document Type: Article

References (61)

1. Hinz B. Formation and function of the myofibroblast during tissue repair. J Invest Dermatol 2007; 127:526-37; PMID:17299435; http://dx.doi.org/10.1038/sj.jid.5700613
2. Wynn TA. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest 2007; 117:524-9; PMID:17332879; http://dx.doi.org/10.1172/JCI31487
3. Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Bio 2002; 3:349-63; http://dx.doi.org/10.1038/nrm809
4. Hinz B, Gabbiani G. Fibrosis: recent advances in myofibroblast biology and new therapeutic perspectives. F1000 Biol Rep 2010; 2:78; PMID:21170369; http://dx.doi.org/10.3410/B2-78
5. Desmouliere A, Darby IA, Gabbiani G. Normal and pathologic soft tissue remodeling: role of the myofibroblast, with special emphasis on liver and kidney fibrosis. Lab Invest 2003; 83:1689-707; PMID:14691287; http://dx.doi.org/10.1097/01.LAB.0000101911.53973.90
6. Biernacka A, Dobaczewski M, Frangogiannis NG. TGF-beta signaling in fibrosis. Growth Factors 2011; 29:196-202; PMID:; http://dx.doi.org/10.3109/08977194.2011.595714
7. Kulozik M, Hogg A, Lankat-Buttgereit B, Krieg T. Colocalization of transforming growth factor beta 2 with alpha 1(I) procollagen mRNA in tissue sections of patients with systemic sclerosis. J Clin Invest 1990; 86:917-22; PMID:1697606; http://dx.doi.org/10.1172/JCI114793
8. Boor P, Floege J. Chronic kidney disease growth factors in renal fibrosis. Clin Exp Pharmacol Physiol 2011; 38:441-50; PMID:21276040; http://dx.doi.org/10.1111/j.1440-1681.2011.05487.x
9. Sime PJ, O'Reilly KM. Fibrosis of the lung and other tissues: new concepts in pathogenesis and treatment. Clin Immunol 2001; 99:308-19; PMID:11358425; http://dx.doi.org/10.1006/clim.2001.5008
10. Gressner AM, Weiskirchen R, Breitkopf K, Dooley S. Roles of TGF-beta in hepatic fibrosis. Front Biosci 2002; 7:d793-807; PMID:11897555; http://dx.doi.org/10.2741/gressner
11. Mori T, Kawara S, Shinozaki M, Hayashi N, Kakinuma T, Igarashi A, Takigawa M, Nakanishi T, Takehara K. Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse fibrosis model. J Cell Physiol 1999; 181:153-9; PMID:10457363; http://dx.doi.org/10.1002/(SICI)1097-4652(199910)181:1%3c153::AID-JCP16%3e3.0.CO;2-K
12. Abreu JG, Ketpura NI, Reversade B, De Robertis EM. Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta. Nat Cell Biol 2002; 4:599-604; PMID:12134160
13. Frazier K, Williams S, Kothapalli D, Klapper H, Grotendorst GR. Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor. J Invest Dermatol 1996; 107:404-11; PMID:8751978; http://dx.doi.org/10.1111/1523-1747.ep12363389
14. Leask A, Parapuram SK, Shi-Wen X, Abraham DJ. Connective tissue growth factor (CTGF, CCN2) gene regulation: a potent clinical bio-marker of fibroproliferative disease? J Cell Commun Signal 2009; 3:89-94; PMID:19156539; http://dx.doi.org/10.1007/s12079-009-0037-7
15. Liu S, Shi-wen X, Abraham DJ, Leask A. CCN2 is required for bleomycin-induced skin fibrosis in mice. Arthritis Rheum 2011; 63:239-46; PMID:20936632; http://dx.doi.org/10.1002/art.30074
16. Phanish MK, Winn SK, Dockrell ME. Connective tissue growth factor-(CTGF, CCN2)-a marker, mediator and therapeutic target for renal fibrosis. Nephron Exp Nephrol 2010; 114:e83-92; PMID:19955828; http://dx.doi.org/10.1159/000262316
17. Igarashi A, Nashiro K, Kikuchi K, Sato S, Ihn H, Fujimoto M, Grotendorst GR, Takehara K. Connective tissue growth factor gene expression in tissue sections from localized scleroderma, keloid, and other fibrotic skin disorders. J Invest Dermatol 1996; 106:729-33; PMID:8618012; http://dx.doi.org/10.1111/1523-1747.ep12345771
18. Huang G, Brigstock DR. Regulation of hepatic stellate cells by connective tissue growth factor. Front Biosci (Landmark Ed) 2012; 17:2495-507; PMID:22652794; http://dx.doi.org/10.2741/4067
19. Laplante P, Sirois I, Raymond MA, Kokta V, Beliveau A, Prat A, Pshezhetsky AV, Hebert MJ. Caspase-3-mediated secretion of connective tissue growth factor by apoptotic endothelial cells promotes fibrosis. Cell Death Differ 2010; 17:291-303; PMID:19730442; http://dx.doi.org/10.1038/cdd.2009.124
20. Hong KH, Yoo SA, Kang SS, Choi JJ, Kim WU, Cho CS. Hypoxia induces expression of connective tissue growth factor in scleroderma skin fibroblasts. Clin Exp Immunol 2006; 146:362-70; PMID:17034590; http://dx.doi.org/10.1111/j.1365-2249.2006.03199.x
21. Higgins DF, Biju MP, Akai Y, Wutz A, Johnson RS, Haase VH. Hypoxic induction of Ctgf is directly mediated by Hif-1. Am J Physiol Renal Physiol 2004; 287:F1223-32; PMID:15315937; http://dx.doi.org/10.1152/ajprenal.00245.2004
22. Braig S, Wallner S, Junglas B, Fuchshofer R, Bosserhoff AK. CTGF is overexpressed in malignant melanoma and promotes cell invasion and migration. Br J Cancer 2011; 105:231-8; PMID:21673687; http://dx.doi.org/10.1038/bjc.2011.226
23. Nazio F, Strappazzon F, Antonioli M, Bielli P, Cianfanelli V, Bordi M, Gretzmeier C, Dengjel J, Piacentini M, Fimia GM, et al. mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat Cell Biol 2013; 15:406-16; PMID:23524951; http://dx.doi.org/10.1038/ncb2708
24. Del Principe D, Lista P, Malorni W, Giammarioli AM. Fibroblast autophagy in fibrotic disorders. J Pathol 2013; 229:208-20; PMID:23018629; http://dx.doi.org/10.1002/path.4115
25. Hernandez-Gea V, Friedman SL. Autophagy fuels tissue fibrogenesis. Autophagy 2012; 8:849-50; PMID:22617442; http://dx.doi.org/10.4161/auto.19947
26. Hernandez-Gea V, Ghiassi-Nejad Z, Rozenfeld R, Gordon R, Fiel MI, Yue Z, Czaja MJ, Friedman SL. Autophagy releases lipid that promotes fibrogenesis by activated hepatic stellate cells in mice and in human tissues. Gastroenterology 2012; 142:938-46; PMID:22240484; http://dx.doi.org/10.1053/j.gastro.2011.12.044
27. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 2012; 8:445-544; PMID:22966490; http://dx.doi.org/10.4161/auto.19496
28. Wu YT, Tan HL, Shui G, Bauvy C, Huang Q, Wenk MR, Ong CN, Codogno P, Shen HM. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J Biol Chem 2010; 285:10850-61; PMID:20123989; http://dx.doi.org/10.1074/jbc.M109.080796
29. Blommaart EF, Krause U, Schellens JP, Vreeling-Sindelarova H, Meijer AJ. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur J Biochem 1997; 243:240-6; PMID:9030745; http://dx.doi.org/10.1111/j.1432-1033.1997.0240a.x
30. Petiot A, Ogier-Denis E, Blommaart EF, Meijer AJ, Codogno P. Distinct classes of phosphatidylinositol 3′-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J Biol Chem 2000; 275:992-8; PMID:10625637; http://dx.doi.org/10.1074/jbc.275.2.992
31. Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I, Ezaki J, Mizushima N, Ohsumi Y, Uchiyama Y, et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol 2005; 169:425-34; PMID:15866887; http://dx.doi.org/10.1083/jcb.200412022
32. Laplante P, Raymond MA, Gagnon G, Vigneault N, Sasseville AMJ, Langelier Y, Bernard M, Raymond Y, Hebert MJ. Novel fibrogenic pathways are activated in response to endothelial apoptosis: Implications in the pathophysiology of systemic sclerosis. J Immunol 2005; 174:5740-9; PMID:15843576; http://dx.doi.org/10.4049/jimmunol.174.9.5740
33. Laplante P, Raymond MA, Labelle A, Abe J, Iozzo RV, Hebert MJ. Perlecan proteolysis induces an alpha2-beta1 integrin- and Src family kinase-dependent antiapoptotic pathway in fibroblasts in the absence of focal adhesion kinase activation. J Biol Chem 2006; 281:30383-92; PMID:16882656; http://dx.doi.org/10.1074/jbc.M606412200
34. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003; 113:685-700; PMID:12809600; http://dx.doi.org/10.1016/S0092-8674(03)00432-X
35. Leask A. CCN2: a bona fide target for anti-fibrotic drug intervention. J Cell Commun Signal 2011; 5:131-3; PMID:21484186; http://dx.doi.org/10.1007/s12079-011-0125-3
36. Brigstock DR. Connective tissue growth factor (CCN2, CTGF) and organ fibrosis: lessons from transgenic animals. J Cell Commun Signal 2010; 4:1-4; PMID:19798591; http://dx.doi.org/10.1007/s12079-009-0071-5
37. Chen G, Chen H, Wang C, Peng Y, Sun L, Liu H, Liu F. Rapamycin ameliorates kidney fibrosis by inhibiting the activation of mTOR signaling in interstitial macrophages and myofibroblasts. PloS One 2012; 7:e33626; PMID:22470459; http://dx.doi.org/10.1371/journal.pone.0033626
38. Huang S, Bjornsti MA, Houghton PJ. Rapamycins: mechanism of action and cellular resistance. Cancer Biol Ther 2003; 2:222-32; PMID:12878853; http://dx.doi.org/10.4161/cbt.2.3.360
39. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM. Prolonged rapamycin treatment inhibits mTORC2 assembly and AktPKB. Mol Cell 2006; 22:159-68; PMID:16603397; http://dx.doi.org/10.1016/j.molcel.2006.03.029
40. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 2012; 149:274-93; PMID:22500797; http://dx.doi.org/10.1016/j.cell.2012.03.017
41. Julien LA, Carriere A, Moreau J, Roux PP. mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling. Mol Cell Biol 2010; 30:908-21; PMID:19995915; http://dx.doi.org/10.1128/MCB.00601-09
42. Iredale JP. Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J Clin Invest 2007; 117:539-48; PMID:17332881; http://dx.doi.org/10.1172/JCI30542
43. Zeisberg M, Neilson EG. Mechanisms of tubulointerstitial fibrosis. J Am Soc Nephrol 2010; 21:1819-34; PMID:20864689; http://dx.doi.org/10.1681/ASN.2010080793
44. Sivakumar P, Ntolios P, Jenkins G, Laurent G. Into the matrix: targeting fibroblasts in pulmonary fibrosis. Curr Opin Pulm Med 2012; 18:462-9; PMID:22847104; http://dx.doi.org/10.1097/MCP.0b013e328356800f
45. Patel AS, Lin L, Geyer A, Haspel JA, An CH, Cao J, Rosas IO, Morse D. Autophagy in idiopathic pulmonary fibrosis. PloS one 2012; 7:e41394; PMID:22815997; http://dx.doi.org/10.1371/journal.pone.0041394
46. Yoshizaki A, Yanaba K, Yoshizaki A, Iwata Y, Komura K, Ogawa F, Takenaka M, Shimizu K, Asano Y, Hasegawa M, et al. Treatment with rapamycin prevents fibrosis in tight-skin and bleomycin-induced mouse models of systemic sclerosis. Arthritis Rheum 2010; 62:2476-87; PMID:20506342; http://dx.doi.org/10.1002/art.27498
47. Grotendorst GR, Okochi H, Hayashi N. A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene. Cell Growth Differ 1996; 7:469-80; PMID:9052988
48. Ponticos M, Holmes AM, Shi-wen X, Leoni P, Khan K, Rajkumar VS, Hoyles RK, Bou-Gharios G, Black CM, Denton CP, et al. Pivotal role of connective tissue growth factor in lung fibrosis: MAPK-dependent transcriptional activation of type I collagen. Arthritis Rheum 2009; 60:2142-55; PMID:19565505; http://dx.doi.org/10.1002/art.24620
49. Lipson KE, Wong C, Teng Y, Spong S. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogenesis Tissue Repair 2012; 5 Suppl 1:S24; PMID:23259531; http://dx.doi.org/10.1186/1755-1536-5-S1-S24
50. Wang Q, Usinger W, Nichols B, Gray J, Xu L, Seeley TW, Brenner M, Guo G, Zhang W, Oliver N, et al. Cooperative interaction of CTGF and TGF-beta in animal models of fibrotic disease. Fibrogenesis Tissue Repair 2011; 4:4; PMID:21284856; http://dx.doi.org/10.1186/1755-1536-4-4
51. Yokoi H, Mukoyama M, Nagae T, Mori K, Suganami T, Sawai K, Yoshioka T, Koshikawa M, Nishida T, Takigawa M, et al. Reduction in connective tissue growth factor by antisense treatment ameliorates renal tubulointerstitial fibrosis. J Am Soc Nephrol 2004; 15:1430-40; PMID:15153554; http://dx.doi.org/10.1097/01.ASN.0000130565.69170.85
52. Li G, Xie Q, Shi Y, Li D, Zhang M, Jiang S, Zhou H, Lu H, Jin Y. Inhibition of connective tissue growth factor by siRNA prevents liver fibrosis in rats. J Gene Med 2006; 8:889-900; PMID:16652398; http://dx.doi.org/10.1002/jgm.894
53. Allen JT, Knight RA, Bloor CA, Spiteri MA. Enhanced insulin-like growth factor binding protein-related protein 2 (Connective tissue growth factor) expression in patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Cell Mol Biol 1999; 21:693-700; PMID:10572066; http://dx.doi.org/10.1165/ajrcmb.21.6.3719
54. Paradis V, Dargere D, Vidaud M, De Gouville AC, Huet S, Martinez V, Gauthier JM, Ba N, Sobesky R, Ratziu V, et al. Expression of connective tissue growth factor in experimental rat and human liver fibrosis. Hepatology 1999; 30:968-76; PMID:10498649; http://dx.doi.org/10.1002/hep.510300425
55. Sato S, Nagaoka T, Hasegawa M, Tamatani T, Nakanishi T, Takigawa M, Takehara K. Serum levels of connective tissue growth factor are elevated in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis. J Rheumatol 2000; 27:149-54; PMID:10648031
56. Metalidis C, van Vuuren SH, Broekhuizen R, Lerut E, Naesens M, Bakker SJ, Wetzels JF, Goldschmeding R, Kuypers DR. Urinary connective tissue growth factor is associated with human renal allograft fibrogenesis. Transplantation 2013; 96:494-500; PMID:23803600; http://dx.doi.org/10.1097/TP.0b013e31829b07e1
57. Cheng O, Thuillier R, Sampson E, Schultz G, Ruiz P, Zhang X, Yuen PS, Mannon RB. Connective tissue growth factor is a biomarker and mediator of kidney allograft fibrosis. Am J Transplant 2006; 6:2292-306; PMID:16889607; http://dx.doi.org/10.1111/j.1600-6143.2006.01493.x
58. Nguyen TQ, Tarnow L, Andersen S, Hovind P, Parving HH, Goldschmeding R, van Nieuwenhoven FA. Urinary connective tissue growth factor excretion correlates with clinical markers of renal disease in a large population of type 1 diabetic patients with diabetic nephropathy. Diabetes Care 2006; 29:83-8; PMID:16373901; http://dx.doi.org/10.2337/diacare.29.01.06.dc05-1670
59. Nayak BK, Feliers D, Sudarshan S, Friedrichs WE, Day RT, New DD, Fitzgerald JP, Eid A, Denapoli T, Parekh DJ, et al. Stabilization of HIF-2alpha through redox regulation of mTORC2 activation and initiation of mRNA translation. Oncogene 2013; 32:3147-55; PMID:22869144; http://dx.doi.org/10.1038/onc.2012.333
60. Araya J, Kojima J, Takasaka N, Ito S, Fujii S, Hara H, Yanagisawa H, Kobayashi K, Tsurushige C, Kawaishi M, et al. Insufficient autophagy in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2013; 304:L56-69; PMID:23087019; http://dx.doi.org/10.1152/ajplung.00213.2012
61. Cailhier JF, Sirois I, Laplante P, Lepage S, Raymond MA, Brassard N, Prat A, Iozzo RV, Pshezhetsky AV, Hebert MJ. Caspase-3 activation triggers extracellular cathepsin L release and endorepellin proteolysis. J Biol Chem 2008; 283:27220-9; PMID:18658137; http://dx.doi.org/10.1074/jbc.M801164200