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Titolo:
A selective ROCK inhibitor, Y27632, prevents dimethylnitrosamine-induced hepatic fibrosis in rats
Autore:
Tada, S; Iwamoto, H; Nakamuta, M; Sugimoto, R; Enjoji, M; Nakashima, Y; Nawata, H;
Indirizzi:
Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, Fukuoka 8128582, Japan Kyushu Univ Fukuoka Japan 8128582 ci, Higashi Ku, Fukuoka 8128582, Japan Kyushu Univ, Grad Sch Med Sci, Dept Pathophysiol & Expt Pathol, Fukuoka 8128582, Japan Kyushu Univ Fukuoka Japan 8128582 & Expt Pathol, Fukuoka 8128582, Japan
Titolo Testata:
JOURNAL OF HEPATOLOGY
fascicolo: 4, volume: 34, anno: 2001,
pagine: 529 - 536
SICI:
0168-8278(200104)34:4<529:ASRIYP>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
GTP-BINDING PROTEIN; RHO-ASSOCIATED KINASE; ACTIN STRESS FIBERS; FOCAL ADHESIONS; CELLS; CYTOSKELETON; EXPRESSION; ACTIVATION; GROWTH; HYPERTENSION;
Keywords:
p160ROCK; Rho; type I collagen; alpha-smooth muscle actin; hepatic stellate cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Nakamuta, M Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan Kyushu Univ 3-1-1 Maidashi Fukuoka Japan 8128582 28582, Japan
Citazione:
S. Tada et al., "A selective ROCK inhibitor, Y27632, prevents dimethylnitrosamine-induced hepatic fibrosis in rats", J HEPATOL, 34(4), 2001, pp. 529-536

Abstract

Background: p160ROCK is a direct Rho target which mediates Rho-induced assembly of focal adhesions and stress fibers. We previously reported that Rhosignaling pathways are involved in the activation of hepatic stellate cells (HSC) in vitro. The aim of the present study was to test the hypothesis that an inhibitor specific for p160ROCK (Y27632) could prevent experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Methods: Y27632 was given orally at 30 mg/kg daily for 4 weeks after the first injection of DMN. The degree of fibrosis was evaluated by image analysis and also by measurements of collagen and hydroxyproline content in the liver. The expression of alpha -smooth muscle actin (alpha -SMA) in the liver and in the primary cultured HSC was also evaluated. Semi-quantitative RT-PCR was performed to evaluate the expression of type I collagen mRNA in theliver. Results: Y27632 treatment significantly decreased the occurrence of DMN-induced hepatic fibrosis and reduced the collagen and hydroxyproline content and alpha -SMA expression in the liver. The expression of alpha -SMA in HSCwas also suppressed in vitro. Conclusions: These findings indicate that inhibitors of the Rho-ROCK pathway might be useful therapeutically in hepatic fibrosis. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 21:50:05