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.
Moriyama
Toshiki
T
Department of Medical Science II, School of Health and Sport Sciences, Osaka University, Osaka, Japan. moriyama@wellness.hss.osaka-u.ac.jp
Nagatoya
Katsuyuki
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D055513:Connective Tissue Growth Factor; D005355:Fibrosis / Q000517:prevention & control; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007674:Kidney Diseases / Q000473:pathology / Q000517:prevention & control*; D007684:Kidney Tubules / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000473:pathology / Q000517:prevention & control; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D054460:rho-Associated Kinases
D000577:Amides; C526317:CCN2 protein, human; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D055513:Connective Tissue Growth Factor; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins; C049347:fasudil