Molecular mechanisms and therapeutic strategies of chronic renal injury: Renoprotective effect of rho-kinase inhibitor in hypertensive glomerulosclerosis

Abstract

Among the GTP-binding proteins, Rho is known to function as a molecular switch in various cellular functions. Among the Rho effectors, the cellular function and signal transduction of Rho-kinase have been extensively studied. However, information about its in vivo functions is still limited. With the recent development of a specific Rho-kinase inhibitor such as Y-27632 and fasudil, the understanding of the role of the Rho/Rho-kinase pathway in vitro and in vivo has advanced. However, to date, there have been few studies investigating the role of Rho-kinase in renal disease. Recent studies have shown that Rho-kinase inhibitor significantly attenuated the tubulointerstitial fibrosis in kidney induced by unilateral ureteral obstruction. However, there have been few studies investigating the role of the Rho/Rho-kinase pathway in hypertensive glomerular sclerosis. In this review, we described the role of the Rho/Rho-kinase pathway in the progression of renal glomerulosclerosis in several forms of hypertensive rats. Our results suggest that chronic inhibition of the Rho-kinase pathway may be a new therapeutic approach for hypertensive glomerulosclerosis. Our results also suggest that the mechanism of the renoprotective effect of Rho-kinase inhibitor is partly mediated via inhibition of extracellular matrix gene expression, monocytes/ macrophages infiltration, oxidative stress, and upregulation of eNOS gene expression. ©2006 The Japanese Pharmacological Society.