Delayed mTOR inhibition with low dose of everolimus reduces TGFβ expression, attenuates proteinuria and renal damage in the renal mass reduction model

PLoS ONE

Volumn 7, Issue 3, 2012, Pages

  Kurdián, Melania ^a   Herrero Fresneda, Inmaculada ^b   Lloberas, Nuria ^b   Gimenez Bonafe, Pepita ^c   Coria, Virginia ^a   Grande, María T ^d   Boggia, José ^a   Malacrida, Leonel ^a   Torras, Joan ^b   Arévalo, Miguel A ^d   González Martínez, Francisco ^a   López Novoa, José M ^e   Grinyó, Josep ^b   Noboa, Oscar ^a  

^a DEPARTAMENTO DE BIOQUÍMICA   (Uruguay)

^b HOSPITAL UNIVERSITARI DE BELLVITGE   (Spain)

^c UNIVERSITY OF BARCELONA   (Spain)

^d UNIVERSITY OF SALAMANCA   (Spain)

^e UNIVERSITY OF SALAMANCA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; EVEROLIMUS; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN KINASE B; TRANSFORMING GROWTH FACTOR BETA; CREATININE; DRUG DERIVATIVE; MTOR PROTEIN, RAT; RAPAMYCIN; TARGET OF RAPAMYCIN KINASE;

ALBUMINURIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD PRESSURE; CELL PROLIFERATION; CONTROLLED STUDY; FIBROBLAST; GENE EXPRESSION; GLOMERULOSCLEROSIS; KIDNEY DISEASE; KIDNEY FIBROSIS; KIDNEY HYPERTROPHY; LOW DRUG DOSE; MALE; NEPHRECTOMY; NONHUMAN; PROTEIN EXPRESSION; PROTEINURIA; RAT; RENAL PROTECTION; TUBULOINTERSTITIAL DAMAGE; TUBULOINTERSTITIAL FIBROSIS; ANALYSIS OF VARIANCE; ANIMAL; BLOOD; DRUG ANTAGONISM; DRUG EFFECT; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IMMUNOHISTOCHEMISTRY; KIDNEY; METABOLISM; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SPECTROPHOTOMETRY; URINE; WESTERN BLOTTING;

ANIMALIA; MAMMALIA; RATTUS NORVEGICUS;

ANALYSIS OF VARIANCE; ANIMALS; BLOTTING, WESTERN; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CREATININE; IMMUNOHISTOCHEMISTRY; KIDNEY; NEPHRECTOMY; PROTEINURIA; RATS; REAL-TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIROLIMUS; SPECTROPHOTOMETRY; TOR SERINE-THREONINE KINASES; TRANSFORMING GROWTH FACTOR BETA;

EID: 84858011505     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0032516     Document Type: Article

References (50)

1. Dunn C, Croom KF, (2006) Everolimus: a review of its use in renal and cardiac transplantation. Drugs 66: 547-570.
2. Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, et al. (2003) The natural history of chronic allograft nephropathy. N Engl J Med 349: 2326-2333.
3. Kaneku HK, Terasaki PI, (2006) Thirty year trend in kidney transplants: UCLA and UNOS Renal Transplant Registry. Clin Transpl 1-27.
4. Ponticelli C, (2008) Can mTOR inhibitors reduce the risk of late kidney allograft failure? Transpl Int 21: 2-10.
5. Li C, Yang CW, (2009) The pathogenesis and treatment of chronic allograft nephropathy. Nat Rev Nephrol.
6. Eddy AA, (2005) Progression in chronic kidney disease. Adv Chronic Kidney Dis 12: 353-365.
7. Grande MT, Lopez-Novoa JM, (2009) Fibroblast activation and myofibroblast generation in obstructive nephropathy. Nat Rev Nephrol 5: 319-328.
8. Nath KA, (1992) Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis 20: 1-17.
9. Strutz F, Muller GA, (2006) Renal fibrosis and the origin of the renal fibroblast. Nephrol Dial Transplant.
10. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM, (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307: 1098-1101.
11. Letavernier E, Legendre C, (2008) mToR inhibitors-induced proteinuria: mechanisms, significance, and management. Transplant Rev (Orlando) 22: 125-130.
12. Diekmann F, Gutierrez-Dalmau A, Lopez S, Cofan F, Esforzado N, et al. (2007) Influence of sirolimus on proteinuria in de novo kidney transplantation with expanded criteria donors: comparison of two CNI-free protocols. Nephrol Dial Transplant 22: 2316-2321.
13. Morales J, Fierro A, Benavente D, Zehnder C, Ferrario M, et al. (2007) Conversion from a calcineurin inhibitor-based immunosuppressive regimen to everolimus in renal transplant recipients: effect on renal function and proteinuria. Transplant Proc 39: 591-593 S0041-1345(06)01573-9.
14. Vollenbroker B, George B, Wolfgart M, Saleem MA, Pavenstadt H, et al. (2009) mTOR regulates expression of slit diaphragm proteins and cytoskeleton structure in podocytes. Am J Physiol Renal Physiol 296: F418-F426.
15. Torras J, Herrero-Fresneda I, Gulias O, Flaquer M, Vidal A, et al. (2009) Rapamycin has dual opposing effects on proteinuric experimental nephropathies: is it a matter of podocyte damage? Nephrol Dial Transplant.
16. Lloberas N, Cruzado JM, Franquesa M, Herrero-Fresneda I, Torras J, et al. (2006) Mammalian target of rapamycin pathway blockade slows progression of diabetic kidney disease in rats. J Am Soc Nephrol 17: 1395-1404.
17. Wittmann S, Daniel C, Braun A, Vogelbacher R, Shimizu F, et al. (2008) The mTOR inhibitor everolimus attenuates the time course of chronic anti-Thy1 nephritis in the rat. Nephron Exp Nephrol 108: e45-e56.
18. Daniel C, Ziswiler R, Frey B, Pfister M, Marti HP, (2000) Proinflammatory effects in experimental mesangial proliferative glomerulonephritis of the immunosuppressive agent SDZ RAD, a rapamycin derivative. Exp Nephrol 8: 52-62.
19. Vogelbacher R, Wittmann S, Braun A, Daniel C, Hugo C, (2007) The mTOR inhibitor everolimus induces proteinuria and renal deterioration in the remnant kidney model in the rat. Transplantation 84: 1492-1499.
20. Ng YY, Huang TP, Yang WC, Chen ZP, Yang AH, et al. (1998) Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int 54: 864-876.
21. Gadola L, Noboa O, Marquez MN, Rodriguez MJ, Nin N, et al. (2004) Calcium citrate ameliorates the progression of chronic renal injury. Kidney Int 65: 1224-1230.
22. Junaid A, Rosenberg ME, Hostetter TH, (1997) Interaction of angiotensin II and TGF-beta 1 in the rat remnant kidney. J Am Soc Nephrol 8: 1732-1738.
23. Diekmann F, Rovira J, Carreras J, Arellano EM, Banon-Maneus E, et al. (2007) Mammalian target of rapamycin inhibition halts the progression of proteinuria in a rat model of reduced renal mass. J Am Soc Nephrol 18: 2653-2660.
24. Rovira J, Arellano EM, Carreras J, Campos B, Vodenik B, et al. (2009) Mammalian target of rapamycin inhibition prevents glomerular hypertrophy in a model of renal mass reduction. Transplantation 88: 646-652.
25. Zafar I, Belibi FA, He Z, Edelstein CL, (2009) Long-term rapamycin therapy in the Han:SPRD rat model of polycystic kidney disease (PKD). Nephrol Dial Transplant 24: 2349-2353.
26. Hay N, Sonenberg N, (2004) Upstream and downstream of mTOR. Genes Dev 18: 1926-1945.
27. Rahimi RA, Andrianifahanana M, Wilkes MC, Edens M, Kottom TJ, et al. (2009) Distinct roles for mammalian target of rapamycin complexes in the fibroblast response to transforming growth factor-beta. Cancer Res 69: 84-93.
28. Taal MW, Chertow GM, Rennke HG, Gurnani A, Jiang T, et al. (2001) Mechanisms underlying renoprotection during renin-angiotensin system blockade. Am J Physiol Renal Physiol 280: F343-F355.
29. Bottinger EP, Bitzer M, (2002) TGF-beta signaling in renal disease. J Am Soc Nephrol 13: 2600-2610.
30. Shihab FS, Bennett WM, Yi H, Choi SO, Andoh TF, (2004) Sirolimus increases transforming growth factor-beta1 expression and potentiates chronic cyclosporine nephrotoxicity. Kidney Int 65: 1262-1271.
31. Wang S, Wilkes MC, Leof EB, Hirschberg R, (2010) Noncanonical TGF-beta pathways, mTORC1 and Abl, in renal interstitial fibrogenesis. Am J Physiol Renal Physiol 298: F142-F149.
32. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, et al. (2006) Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 22: 159-168.
33. Lieberthal W, Levine JS, (2009) The role of the mammalian target of rapamycin (mTOR) in renal disease. J Am Soc Nephrol 20: 2493-2502.
34. Lieberthal W, Fuhro R, Andry CC, Rennke H, Abernathy VE, et al. (2001) Rapamycin impairs recovery from acute renal failure: role of cell-cycle arrest and apoptosis of tubular cells. Am J Physiol Renal Physiol 281: F693-F706.
35. McTaggart RA, Gottlieb D, Brooks J, Bacchetti P, Roberts JP, et al. (2003) Sirolimus prolongs recovery from delayed graft function after cadaveric renal transplantation. Am J Transplant 3: 416-423. 078.
36. Letavernier E, Bruneval P, Mandet C, Van Huyen JP, Peraldi MN, et al. (2007) High sirolimus levels may induce focal segmental glomerulosclerosis de novo. Clin J Am Soc Nephrol 2: 326-333.
37. Nakagawa S, Masuda S, Nishihara K, Inui K, (2010) mTOR inhibitor everolimus ameliorates progressive tubular dysfunction in chronic renal failure rats. Biochem Pharmacol 79: 67-76.
38. Bonegio RG, Fuhro R, Wang Z, Valeri CR, Andry C, et al. (2005) Rapamycin ameliorates proteinuria-associated tubulointerstitial inflammation and fibrosis in experimental membranous nephropathy. J Am Soc Nephrol 16: 2063-2072.
39. Rangan GK, Coombes JD, (2007) Renoprotective effects of sirolimus in non-immune initiated focal segmental glomerulosclerosis. Nephrol Dial Transplant 22: 2175-2182.
40. Wu MJ, Wen MC, Chiu YT, Chiou YY, Shu KH, et al. (2006) Rapamycin attenuates unilateral ureteral obstruction-induced renal fibrosis. Kidney Int 69: 2029-2036.
41. Tao Y, Kim J, Schrier RW, Edelstein CL, (2005) Rapamycin markedly slows disease progression in a rat model of polycystic kidney disease. J Am Soc Nephrol 16: 46-51.
42. Kramer S, Wang-Rosenke Y, Scholl V, Binder E, Loof T, et al. (2008) Low-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1-induced chronic glomerulosclerosis of the rat. Am J Physiol Renal Physiol 294: F440-F449.
43. Turpeinen U, Koivunen E, Stenman UH, (1987) Liquid-chromatographic determination of beta 2-microglobulin, alpha 1-acid glycoprotein, and albumin in urine. Clin Chem 33: 1756-1760.
44. Zhang G, Oldroyd SD, Huang LH, Yang B, Li Y, et al. (2001) Role of apoptosis and Bcl-2/Bax in the development of tubulointerstitial fibrosis during experimental obstructive nephropathy. Exp Nephrol 9: 71-80.
45. Veniant M, Heudes D, Clozel JP, Bruneval P, Menard J, (1994) Calcium blockade versus ACE inhibition in clipped and unclipped kidneys of 2K-1C rats. Kidney Int 46: 421-429.
46. Masseroli M, O'Valle F, Andujar M, Ramirez C, Gomez-Morales M, et al. (1998) Design and validation of a new image analysis method for automatic quantification of interstitial fibrosis and glomerular morphometry. Lab Invest 78: 511-522.
47. Flores O, Arevalo M, Gallego B, Hidalgo F, Vidal S, et al. (1998) Beneficial effect of the long-term treatment with the combination of an ACE inhibitor and a calcium channel blocker on renal injury in rats with 5/6 nephrectomy. Exp Nephrol 6: 39-49.
48. Schanstra JP, Neau E, Drogoz P, Arevalo Gomez MA, Lopez Novoa JM, et al. (2002) In vivo bradykinin B2 receptor activation reduces renal fibrosis. J Clin Invest 110: 371-379.
49. Grande MT, Fuentes-Calvo I, Arevalo M, Heredia F, Santos E, et al. (2010) Deletion of H-Ras decreases renal fibrosis and myofibroblast activation following ureteral obstruction in mice. Kidney Int 77: 509-518.
50. Herrero-Fresneda I, Torras J, Lloberas N, Riera M, Cruzado JM, et al. (2000) Cold ischemia in the absence of alloreactivity induces chronic transplant nephropathy through a process mediated by the platelet-activating factor. Transplantation 70: 1624-1631.