The Rho-ROCK system as a new therapeutic target for preventing interstitial fibrosis.

The small GTPase Rho is involved in cell-to-substratum adhesion and cell contraction. These actions of Rho mediated by downstream Rho effectors such as Rho-associated coiled-coil forming protein kinase (ROCK) may be partly responsible for the progression of renal interstitial fibrosis. A body of evidence has been accumulated with regard to the involvement of the Rho-ROCK signaling pathway in the development of fibrotic lesions in various organs including the kidney. Tubulointerstitial fibrosis is a final common pathway to the eventual structural desolation of kidneys, and therefore is an important therapeutic target to cure or reverse the progressive functional deterioration. In this review, we will highlight the possible involvement of the Rho-ROCK signaling pathway in the pathogenesis of tubulointerstitial fibrosis and discuss the therapeutic approach toward tubulointerstitial fibrosis by the inhibition of the Rho-ROCK pathway. (c) 2004 Prous Science. All rights reserved.