• 四川大學(xué)華西醫(yī)院腎臟內(nèi)科（成都，610041）;

【摘要】　 RhoA/Rho相關(guān)卷曲螺旋形成的蛋白激酶（ROCK）信號通路是細胞內(nèi)重要的信號轉(zhuǎn)導(dǎo)通路，在慢性腎臟疾病的進展中起重要作用。腎間質(zhì)纖維化是各種慢性腎臟疾病發(fā)展到終末期腎衰竭的共同途徑；糖尿病腎病是繼發(fā)性慢性腎臟疾病的主要病因?，F(xiàn)就RhoA/ROCK信號通路在腎間質(zhì)纖維化和糖尿病腎病發(fā)病機制中的作用作一綜述。

引用本文： 柳飛,付平. RhoA/Rho相關(guān)卷曲螺旋形成的蛋白激酶信號通路與慢性腎臟疾病. 華西醫(yī)學(xué), 2011, 26(5): 781-783. doi: 復(fù)制

1. 　Riento K, Ridley AJ. Rocks: multifunctional kinases in cell behaviour[J]. Nat Rev Mol Cell Biol, 2003, 4(6): 446-456.
2. 　Shibuya M, Hirai S, Seto M, et al. Effects of fasudil in acute ischemic stroke: results of a prospective placebo-controlled double-blind trial[J]. J Neurol Sci, 2005, 238(1-2): 31-39.
3. 　Noma K, Oyama N, Liao JK. Physiological role of ROCKs in the cardiovascular system [J]. Am J Physiol Cell Physiol, 2006, 290(3): C661-C668.
4. 　Shi J, Zhan L, Wei L. Rho-kinase in development and heart failure: insights from genetic models[J]. Pediatr Cardiol, 2011, 32(3): 297-304.
5. 　Bar-Sagi D, Hall A. Ras and Rho GTPases: a family reunion[J]. Cell, 2000, 103(2): 227-238.
6. 　Di Cunto F, Imarisio S, Hirsch E, et al. Defective neurogenesis in citron kinase knockout mice by altered cytokinesis and massive apoptosis[J]. Neuron, 2000, 28(1): 115-127.
7. 　Loirand G, Guérin P, Pacaud P. Rho kinases in cardiovascular physiology and pathophysiology[J]. Circ Res, 2006, 98(3): 322-334.
8. 　Razzaque MS, Taguchi T. Cellular and molecular events leading to renal tubulointerstitial fibrosis[J]. Med Electron Microse, 2002, 35 (2): 68 - 80.
9. 　Negri AL. Prevention of progressive fibrosis in chronic renal diseases: antifibrotic agents[J]. J Nephol, 2004, 17(4): 496-503.
10. 　Liu Y. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention[J]. J Am Soc Nephrol, 2004, 15 (1): 1-12.
11. 　Rastaldi MP, Ferrario F, Giardino L, et al . Epithelial - mesenchymal transition of tubular epithelial cells in human renal biopsies[J]. Kidney Int, 2002, 62(1): 137-146.
12. 　Lan HY. Tubular epithelial-myofibroblast transdifferentiation mechanisms in proximal tubule cells[J].Curr Opin Nephrol Hypertens, 2003, 12(1): 25-29.
13. 　Bhowmick NA, Ghiassi M, Bakin A, et al . Trans forming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism[J]. Mol Biol Cell, 2001, 12 (1): 27-36.
14. 　Tian YC, Fraser D, Attisano L, et al. TGF - betal - mediated alteration of renal proximal tubular epithelial cell phenotype[J]. Am J Physiol Renal Physiol, 2003, 285 (1): 130-142.
15. 　Nagatoya K, Moriyama T, Kawada N, et al . Y-27632 prevents tubulointerstitial fibrosis in mouse kidney with unilateral ureteral obstruction[J]. Kidney Int, 2002, 61 (5): 1684 -169.
16. 　Takeda Y, Nishikimi T, Akimoto K, et al. Beneficial effects of a combination of Rho-kinase inhibitor and ACE inhibitor on tubulointerstitial fibrosis induced by unilateral ureteral obstruction[J]. Hyperten Res, 2010, 33 (9): 965-973.
17. 　Jones CA, Krolewski AS, Rogus J, et al. Epidemic of end-stage renal disease in people with diabetes in the United States population: do we know cause?[J]. Kidney Int, 2005, 67 (5): 1684-1691.
18. 　Danesh FR, Sadeghi MM,Amro N, et al. 3 - Hydroxy - 3 -methylglutaryl CoA reductase inhibitors prevent high glucose -induced proliferation of mesangial cells via modulation of Rho GTPase/p21 signaling pathway: implications for diabetic nephropathy[J]. Proc Natl Acad Sci USA, 2002, 99 (12): 8301-8305.
19. 　Zeng L, Xu H, Chew TL, et al. HMG CoA reductase inhibition modulates VEGF - induced endothelial cell hyperpermeability by preventing RhoA activation and myosin regulatory light chain phosphorylation[J]. FASEB J, 2005, 19(13): 1845- 1847.
20. 　Fibbi B, Morelli A, Marini M, et al. Atorvastatin but not elocalcitol increases sildenafil responsiveness in spontaneously hypertensive rats by regulating the RhoA/ROCK pathway[J]. J Androl, 2008, 29(1): 70-84.
21. 　Gojo A, Utsunomiya K, Taniguchi K, et al. The Rho-kinase inhibitor, fasudil, attenuates diabetic nephropathy in streptozotocin-induced diabetic rats[J]. Eur J Pharmacol, 2007, 568(1-3): 242-247.
22. 　Kikuchi Y, Yamada M, Imakiire T, et al. A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin - resistant diabetic rats[J]. J Endocrinol, 2007, 192(3): 595-603.
23. 　Kolavennu V, Zeng L, Peng H, et al. Targeting of RhoA/ROCK signaling ameliorates progressionof diabetic nephropathy independent of glucose control[J]. Diabetes, 2008, 57(3): 714-723.
24. 　Peng F, Wu D, Gao B, et al. RhoA/Rho-kinase contribute to the pathogenesis of diabetic renal disease[J]. Diabetes, 2008, 57(6): 1683-1692.
  1. 1. 　Riento K, Ridley AJ. Rocks: multifunctional kinases in cell behaviour[J]. Nat Rev Mol Cell Biol, 2003, 4(6): 446-456.
  2. 2. 　Shibuya M, Hirai S, Seto M, et al. Effects of fasudil in acute ischemic stroke: results of a prospective placebo-controlled double-blind trial[J]. J Neurol Sci, 2005, 238(1-2): 31-39.
  3. 3. 　Noma K, Oyama N, Liao JK. Physiological role of ROCKs in the cardiovascular system [J]. Am J Physiol Cell Physiol, 2006, 290(3): C661-C668.
  4. 4. 　Shi J, Zhan L, Wei L. Rho-kinase in development and heart failure: insights from genetic models[J]. Pediatr Cardiol, 2011, 32(3): 297-304.
  5. 5. 　Bar-Sagi D, Hall A. Ras and Rho GTPases: a family reunion[J]. Cell, 2000, 103(2): 227-238.
  6. 6. 　Di Cunto F, Imarisio S, Hirsch E, et al. Defective neurogenesis in citron kinase knockout mice by altered cytokinesis and massive apoptosis[J]. Neuron, 2000, 28(1): 115-127.
  7. 7. 　Loirand G, Guérin P, Pacaud P. Rho kinases in cardiovascular physiology and pathophysiology[J]. Circ Res, 2006, 98(3): 322-334.
  8. 8. 　Razzaque MS, Taguchi T. Cellular and molecular events leading to renal tubulointerstitial fibrosis[J]. Med Electron Microse, 2002, 35 (2): 68 - 80.
  9. 9. 　Negri AL. Prevention of progressive fibrosis in chronic renal diseases: antifibrotic agents[J]. J Nephol, 2004, 17(4): 496-503.
  10. 10. 　Liu Y. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention[J]. J Am Soc Nephrol, 2004, 15 (1): 1-12.
  11. 11. 　Rastaldi MP, Ferrario F, Giardino L, et al . Epithelial - mesenchymal transition of tubular epithelial cells in human renal biopsies[J]. Kidney Int, 2002, 62(1): 137-146.
  12. 12. 　Lan HY. Tubular epithelial-myofibroblast transdifferentiation mechanisms in proximal tubule cells[J].Curr Opin Nephrol Hypertens, 2003, 12(1): 25-29.
  13. 13. 　Bhowmick NA, Ghiassi M, Bakin A, et al . Trans forming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism[J]. Mol Biol Cell, 2001, 12 (1): 27-36.
  14. 14. 　Tian YC, Fraser D, Attisano L, et al. TGF - betal - mediated alteration of renal proximal tubular epithelial cell phenotype[J]. Am J Physiol Renal Physiol, 2003, 285 (1): 130-142.
  15. 15. 　Nagatoya K, Moriyama T, Kawada N, et al . Y-27632 prevents tubulointerstitial fibrosis in mouse kidney with unilateral ureteral obstruction[J]. Kidney Int, 2002, 61 (5): 1684 -169.
  16. 16. 　Takeda Y, Nishikimi T, Akimoto K, et al. Beneficial effects of a combination of Rho-kinase inhibitor and ACE inhibitor on tubulointerstitial fibrosis induced by unilateral ureteral obstruction[J]. Hyperten Res, 2010, 33 (9): 965-973.
  17. 17. 　Jones CA, Krolewski AS, Rogus J, et al. Epidemic of end-stage renal disease in people with diabetes in the United States population: do we know cause?[J]. Kidney Int, 2005, 67 (5): 1684-1691.
  18. 18. 　Danesh FR, Sadeghi MM,Amro N, et al. 3 - Hydroxy - 3 -methylglutaryl CoA reductase inhibitors prevent high glucose -induced proliferation of mesangial cells via modulation of Rho GTPase/p21 signaling pathway: implications for diabetic nephropathy[J]. Proc Natl Acad Sci USA, 2002, 99 (12): 8301-8305.
  19. 19. 　Zeng L, Xu H, Chew TL, et al. HMG CoA reductase inhibition modulates VEGF - induced endothelial cell hyperpermeability by preventing RhoA activation and myosin regulatory light chain phosphorylation[J]. FASEB J, 2005, 19(13): 1845- 1847.
  20. 20. 　Fibbi B, Morelli A, Marini M, et al. Atorvastatin but not elocalcitol increases sildenafil responsiveness in spontaneously hypertensive rats by regulating the RhoA/ROCK pathway[J]. J Androl, 2008, 29(1): 70-84.
  21. 21. 　Gojo A, Utsunomiya K, Taniguchi K, et al. The Rho-kinase inhibitor, fasudil, attenuates diabetic nephropathy in streptozotocin-induced diabetic rats[J]. Eur J Pharmacol, 2007, 568(1-3): 242-247.
  22. 22. 　Kikuchi Y, Yamada M, Imakiire T, et al. A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin - resistant diabetic rats[J]. J Endocrinol, 2007, 192(3): 595-603.
  23. 23. 　Kolavennu V, Zeng L, Peng H, et al. Targeting of RhoA/ROCK signaling ameliorates progressionof diabetic nephropathy independent of glucose control[J]. Diabetes, 2008, 57(3): 714-723.
  24. 24. 　Peng F, Wu D, Gao B, et al. RhoA/Rho-kinase contribute to the pathogenesis of diabetic renal disease[J]. Diabetes, 2008, 57(6): 1683-1692.