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J Hepatol. 2001 Oct;35(4):474-81.

Inhibitory effect of Y-27632, a ROCK inhibitor, on progression of rat liver fibrosis in association with inactivation of hepatic stellate cells.

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  • 1Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Japan. tmura@kuhp.kyoto-u.ac.jp

Abstract

BACKGROUND/AIMS:

Activation of hepatic stellate cells (HSCs) is a final common pathway of liver fibrosis. Recently, it has been demonstrated that the small GTPase Rho is involved in HSCs activation, and that Y-27632, an inhibitor of Rho-kinase which is an effector that acts downstream of Rho, inhibits Rho-associated effects. The objective of the current study was to investigate the inhibitory effects of Y-27632 on the activation of HSCs and the progression of liver fibrosis.

METHODS:

Y-27632 (1, 10, 100 microM) was added to HSCs isolated from normal rat liver.

RESULTS:

HSCs maintained the 'star-like' configuration of the quiescent stage in the presence of Y-27632, as well as inhibition of the expression of Na+/Ca2+ exchanger mRNA which was reported to be an indicator of HSCs activation. In addition, when Y-27632 (30 mg/kg body weight) was administered to rats with carbon tetrachloride-induced liver fibrosis, collagen deposition was inhibited, the hepatic hydroxyproline content was decreased, and the serum hyaluronic acid level was reduced. Moreover, Y-27632 reduced the number of smooth muscle alpha-actin-positive cells and transforming growth factor-beta1-positive cells, and inhibited the expression of Na/Ca2+ exchanger mRNA.

CONCLUSIONS:

These findings indicate that Y-27632 may be useful for the clinical management of liver fibrosis.

PMID:
11682031
[PubMed - indexed for MEDLINE]
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