Rheb/mTORC1 signaling promotes kidney fibroblast activation and fibrosis

Journal of the American Society of Nephrology

Volumn 24, Issue 7, 2013, Pages 1114-1126

  Jiang, Lei ^a   Xu, Lingling ^a   Mao, Junhua ^a   Li, Jianzhong ^a   Fang, Li ^a   Zhou, Yang ^a   Liu, Wei ^b   He, Weichun ^a   Zijian Zhao, Allan ^c,d   Yang, Junwei ^a   Dai, Chunsun ^a,d  

^a THE SECOND AFFILIATED HOSPITAL OF NANJING MEDICAL UNIVERSITY   (China)

^b SECOND MILITARY MEDICAL UNIVERSITY   (China)

^c NANJING MEDICAL UNIVERSITY   (China)

^d Nanjing Medical University   (China)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; RAPAMYCIN; RHEB PROTEIN; SMALL INTERFERING RNA; TRANSFORMING GROWTH FACTOR BETA1;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL ACTIVATION; CONTROLLED STUDY; FIBROBLAST; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; INHIBITION KINETICS; KIDNEY CELL; KIDNEY FIBROSIS; KIDNEY INTERSTITIUM; KIDNEY PARENCHYMA; MACROPHAGE; MALE; MOUSE; MYOFIBROBLAST; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; RAT; REAL TIME POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; URETER OBSTRUCTION; WESTERN BLOTTING;

EID: 84879951583     PISSN: 10466673     EISSN: 15333450     Source Type: Journal    
DOI: 10.1681/ASN.2012050476     Document Type: Article

References (60)

1. Liu Y: Cellular and molecular mechanisms of renal fibrosis. Nat Rev Nephrol 7: 684-696, 2011
2. Hewitson TD: Renal tubulointerstitial fibrosis: Common but never simple. Am J Physiol Renal Physiol 296: F1239-F1244, 2009
3. Duffield JS, Humphreys BD: Origin of new cells in the adult kidney: Results fromgenetic labeling techniques. Kidney Int 79: 494-501, 2011
4. Eddy AA: Molecular insights into renal interstitial fibrosis. J Am Soc Nephrol 7: 2495-2508, 1996
5. Piera-Velazquez S, Li Z, Jimenez SA: Role of endothelial-mesenchymal transition (EndoMT) in the pathogenesis of fibrotic disorders. Am J Pathol 179: 1074-1080, 2011
6. Quaggin SE, Kapus A: Scar wars: Mapping the fate of epithelialmesenchymal-myofibroblast transition. Kidney Int 80: 41-50, 2011
7. Lemley KV, Kriz W: Anatomy of the renal interstitium. Kidney Int 39: 370-381, 1991
8. Hu K, Lin L, Tan X, Yang J, Bu G, Mars WM, Liu Y: tPA protects renal interstitial fibroblasts and myofibroblasts from apoptosis. J Am Soc Nephrol 19: 503-514, 2008
9. Chevalier RL, Forbes MS, Thornhill BA: Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy. Kidney Int 75: 1145-1152, 2009
10. Yang L, Besschetnova TY, Brooks CR, Shah JV, Bonventre JV: Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med 16: 535-543, 2010
11. HeW, Dai C, Li Y, Zeng G, Monga SP, Liu Y:Wnt/beta-catenin signaling promotes renal interstitial fibrosis. J Am Soc Nephrol 20: 765-776, 2009
12. LieberthalW, Levine JS: The role of the mammalian target of rapamycin (mTOR) in renal disease. J Am Soc Nephrol 20: 2493-2502, 2009
13. Ding H, Zhou D, Hao S, Zhou L, He W, Nie J, Hou FF, Liu Y: Sonic hedgehog signaling mediates epithelial-mesenchymal communication and promotes renal fibrosis. J Am Soc Nephrol 23: 801-813, 2012
14. Barnes JL,Gorin Y:Myofibroblast differentiation during fibrosis: Role of NAD(P)H oxidases. Kidney Int 79: 944-956, 2011
15. Ghosh AK, Vaughan DE: PAI-1 in tissue fibrosis.JCell Physiol 227: 493-507, 2012
16. Hao S, Shen H, Hou Y,MarsWM, Liu Y: tPA is a potentmitogen for renal interstitial fibroblasts: Role of beta1 integrin/focal adhesion kinase signaling. Am J Pathol 177: 1164-1175, 2010
17. Bai X, Ma D, Liu A, Shen X, Wang QJ, Liu Y, Jiang Y: Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38. Science 318: 977-980, 2007
18. Lucchesi PA: Rapamycin plays a new role as differentiator of vascular smooth muscle phenotype. focus on "The mTOR/p70 S6K1 pathway regulates vascular smooth muscle differentiation". Am J Physiol Cell Physiol 286: C480-C481, 2004
19. Ma J,Meng Y, Kwiatkowski DJ, Chen X, Peng H, SunQ, Zha X, Wang F, Wang Y, Jing Y, Zhang S, Chen R, Wang L, Wu E, Cai G, Malinowska-Kolodziej I, Liao Q, Liu Y, Zhao Y, Sun Q, Xu K, Dai J, Han J, Wu L, Zhao RC, ShenH, Zhang H:Mammalian target of rapamycin regulatesmurine and human cell differentiation through STAT3/p63/Jagged/Notch cascade. J Clin Invest 120: 103-114, 2010
20. Ma XM, Blenis J: Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 10: 307-318, 2009
21. Goorden SM, Hoogeveen-Westerveld M, Cheng C, vanWoerden GM, MozaffariM, Post L,Duckers HJ,NellistM, Elgersma Y: Rheb is essential for murine development. Mol Cell Biol 31: 1672-1678, 2011
22. Narita M, Young AR, Arakawa S, Samarajiwa SA, Nakashima T, Yoshida S, Hong S, Berry LS, Reichelt S, FerreiraM, Tavare S, Inoki K, Shimizu S, Narita M: Spatial coupling of mTOR and autophagy augments secretory phenotypes. Science 332: 966-970, 2011
23. Zhang H, Cicchetti G, Onda H, Koon HB, Asrican K, Bajraszewski N, Vazquez F, Carpenter CL, Kwiatkowski DJ: Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR. J Clin Invest 112: 1223-1233, 2003
24. Crino PB, Nathanson KL, Henske EP: The tuberous sclerosis complex. N Engl JMed 355: 1345-1356, 2006
25. McMahon G, Weir MR, Li XC, Mandelbrot DA: The evolving role of mTOR inhibition in transplantation tolerance. J Am Soc Nephrol 22: 408-415, 2011
26. Niedermeier M, Reich B, Rodriguez Gomez M, Denzel A, Schmidbauer K, Göbel N, Talke Y, Schweda F, Mack M: CD4+ T cells control the differentiation of Gr1+ monocytes into fibrocytes. Proc Natl Acad Sci U S A 106: 17892-17897, 2009
27. Proud CG: mTOR signalling in health and disease. Biochem Soc Trans 39: 431-436, 2011
28. Sengupta S, Peterson TR, Sabatini DM: Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell 40: 310-322, 2010
29. Dazert E, Hall MN: mTOR signaling in disease. Curr Opin Cell Biol 23: 744-755, 2011
30. Lloberas N, Cruzado JM, Franquesa M, Herrero-Fresneda I, Torras J, Alperovich G, Rama I, Vidal A, Grinyó JM: Mammalian target of rapamycin pathway blockade slows progression of diabetic kidney disease in rats. J Am Soc Nephrol 17: 1395-1404, 2006
31. Novalic Z, van der Wal AM, Leonhard WN, Koehl G, Breuning MH, Geissler EK, de Heer E, Peters DJ: Dose-dependent effects of sirolimus on mTOR signaling and polycystic kidney disease. J Am Soc Nephrol 23: 842-853, 2012
32. Perico N, Antiga L, Caroli A, Ruggenenti P, Fasolini G, CafaroM,Ondei P, Rubis N, Diadei O, Gherardi G, Prandini S, Panozo A, Bravo RF, Carminati S, De Leon FR, Gaspari F, Cortinovis M, Motterlini N, Ene-Iordache B, Remuzzi A, Remuzzi G: Sirolimus therapy to halt the progression of ADPKD. J Am Soc Nephrol 21: 1031-1040, 2010
33. Qin S, TaglientiM,Nauli SM, Contrino L, Takakura A, Zhou J, Kreidberg JA: Failure to ubiquitinate c-Met leads to hyperactivation of mTOR signaling in a mouse model of autosomal dominant polycystic kidney disease. J Clin Invest 120: 3617-3628, 2010
34. Weimbs T: Polycystic kidney disease and renal injury repair: Common pathways, fluid flow, and the function of polycystin-1. Am J Physiol Renal Physiol 293: F1423-F1432, 2007
35. Habib SL, Yadav M, Tizani S, Bhandari B, Valente AJ: Tuberin inhibits production of the matrix protein fibronectin in diabetes. J Am Soc Nephrol 23: 1652-1662, 2012
36. Shegogue D, Trojanowska M: Mammalian target of rapamycin positively regulates collagen type I production via a phosphatidylinositol 3-kinase-independent pathway. J Biol Chem279: 23166-23175, 2004
37. Sola-Villa D, Camacho M, Sola R, Soler M, Diaz JM, Vila L: IL-1beta induces VEGF, independently of PGE2 induction, mainly through the PI3-K/mTOR pathway in renal mesangial cells. Kidney Int 70: 1935-1941, 2006
38. Vollenbröker B, George B, Wolfgart M, Saleem MA, Pavenstadt H, Weide T: mTOR regulates expression of slit diaphragm proteins and cytoskeleton structure in podocytes. Am J Physiol Renal Physiol 296: F418-F426, 2009
39. Wang S, Wilkes MC, Leof EB, Hirschberg R: Noncanonical TGF-beta pathways, mTORC1 and Abl, in renal interstitial fibrogenesis. Am J Physiol Renal Physiol 298: F142-F149, 2010
40. Chen JK, Chen J, Neilson EG, Harris RC: Role of mammalian target of rapamycin signaling in compensatory renal hypertrophy. J Am Soc Nephrol 16: 1384-1391, 2005
41. Lieberthal W, Levine JS: Mammalian target of rapamycin and the kidney. II. Pathophysiology and therapeutic implications. Am J Physiol Renal Physiol 303: F180-F191, 2012
42. Huber TB, Walz G, Kuehn EW: mTOR and rapamycin in the kidney: Signaling and therapeutic implications beyond immunosuppression. Kidney Int 79: 502-511, 2011
43. Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg MA, Hall A, Hall MN: Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 6: 1122-1128, 2004
44. Barnes EA, Kenerson HL, Jiang X, Yeung RS: Tuberin regulates Ecadherin localization: Implications in epithelial-mesenchymal transition. Am J Pathol 177: 1765-1778, 2010
45. Kato H, Nakajima S, Saito Y, Takahashi S, Katoh R, Kitamura M: mTORC1 serves ER stress-triggered apoptosis via selective activation of the IRE1-JNK pathway. Cell Death Differ 19: 310-320, 2012
46. Li S, Takeuchi F,Wang JA, Fan Q, Komurasaki T, Billings EM, Pacheco-Rodriguez G, Moss J, Darling TN: Mesenchymal-epithelial interactions involving epiregulin in tuberous sclerosis complex hamartomas. Proc Natl Acad Sci U S A 105: 3539-3544, 2008
47. Bell PD, Fitzgibbon W, Sas K, Stenbit AE, AmriaM, Houston A, Reichert R, Gilley S, Siegal GP, Bissler J, Bilgen M, Chou PC, Guay-Woodford L, Yoder B, Haycraft CJ, Siroky B: Loss of primary cilia upregulates renal hypertrophic signaling and promotes cystogenesis. J Am Soc Nephrol 22: 839-848, 2011
48. Inoki K, Mori H, Wang J, Suzuki T, Hong S, Yoshida S, Blattner SM, Ikenoue T, Ruegg MA, Hall MN, Kwiatkowski DJ, Rastaldi MP, Huber TB, KretzlerM, Holzman LB,Wiggins RC, Guan KL: mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice. J Clin Invest 121: 2181-2196, 2011
49. 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 7: e33626, 2012
50. Ballou LM, Lin RZ: Rapamycin and mTOR kinase inhibitors. J ChemBiol 1: 27-36, 2008
51. Inoki K, Huber TB: Mammalian target of rapamycin signaling in the podocyte. Curr Opin Nephrol Hypertens 21: 251-257, 2012
52. Liu Y: Rapamycin and chronic kidney disease: Beyond the inhibition of inflammation. Kidney Int 69: 1925-1927, 2006
53. Zhang H, Bajraszewski N, Wu E, Wang H, Moseman AP, Dabora SL, Griffin JD, Kwiatkowski DJ: PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. J Clin Invest 117: 730-738, 2007
54. Österreicher CH, Penz-Österreicher M, Grivennikov SI, Guma M, Koltsova EK, Datz C, Sasik R, Hardiman G, Karin M, Brenner DA: Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver. Proc Natl Acad Sci U S A 108: 308-313, 2011
55. Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG: Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 110: 341-350, 2002
56. Mori H, Inoki K, Munzberg H, Opland D, Faouzi M, Villanueva EC, Ikenoue T, Kwiatkowski D, MacDougald OA, Myers MG Jr, Guan KL: Critical role for hypothalamic mTOR activity in energy balance. Cell Metab 9: 362-374, 2009
57. Grupp C,Muller GA: Renal fibroblast culture. Exp Nephrol 7: 377-385, 1999
58. Scheele JS, Rhee JM, Boss GR: Determination of absolute amounts of GDP and GTP bound to Ras in mammalian cells: Comparison of parental and Ras-overproducing NIH 3T3 fibroblasts. Proc Natl Acad Sci U S A 92: 1097-1100, 1995
59. ImE, von Lintig FC, Chen J, Zhuang S,Qui W, Chowdhury S,Worley PF, Boss GR, Pilz RB: Rheb is in a high activation state and inhibits B-Raf kinase in mammalian cells. Oncogene 21: 6356-6365, 2002
60. López-De León A, Rojkind M: A simple micromethod for collagen and total protein determination in formalin-fixed paraffin-embedded sections. J Histochem Cytochem 33: 737-743, 1985