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Titolo:
Contribution of small GTPase Rho and its target protein ROCK in a murine model of lung fibrosis
Autore:
Shimizu, Y; Dobashi, K; Iizuka, K; Horie, T; Suzuki, K; Tukagoshi, H; Nakazawa, T; Nakazato, Y; Mori, M;
Indirizzi:
Gunma Univ, Sch Med, Fac Med, Dept Internal Med 1, Maebashi, Gumma 3718511, Japan Gunma Univ Maebashi Gumma Japan 3718511 1, Maebashi, Gumma 3718511, Japan Gunma Univ, Sch Hlth Sci, Gunma, Japan Gunma Univ Gunma JapanGunma Univ, Sch Hlth Sci, Gunma, Japan Gunma Univ, Sch Med, Dept Pathol 1, Gunma, Japan Gunma Univ Gunma JapanGunma Univ, Sch Med, Dept Pathol 1, Gunma, Japan
Titolo Testata:
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
fascicolo: 1, volume: 163, anno: 2001,
pagine: 210 - 217
SICI:
1073-449X(200101)163:1<210:COSGRA>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
IDIOPATHIC PULMONARY FIBROSIS; MACROPHAGE CELL-LINE; SMOOTH-MUSCLE; MH-S; KINASE; BLEOMYCIN; RECEPTOR; MICE; SENSITIZATION; ACCUMULATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Iizuka, K Gunma Univ, Sch Med, Fac Med, Dept Internal Med 1, 3-39-15 ShowaMachi, Maebashi, Gumma 3718511, Japan Gunma Univ 3-39-15 Showa Machi Maebashi Gumma Japan 3718511 apan
Citazione:
Y. Shimizu et al., "Contribution of small GTPase Rho and its target protein ROCK in a murine model of lung fibrosis", AM J R CRIT, 163(1), 2001, pp. 210-217

Abstract

Excess fibroblasts and inflammatory cells may play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The small GTPase, Rho, and its target protein, Rho-associated coiled-coil-forming protein kinase (ROCK), have been recognized to be major regulators of cell locomotion mediated by reorganization of the actin cytoskelton. Activated ROCK inhibits myosin phosphatase, and this in turn induces phosphorylation of the myosin light chain (MLC). To determine the mechanisms underlying the deteriorationprocess of IPF, we investigated the effect of Y-27632, a selective ROCK inhibitor, in a murine model of bleomycin (BLM)-induced lung fibrosis. The Aschcroft score and hydroxyproline content of the BLM-treated mouse lung decreased in response to Y-27632 treatment. The number of broncoalveolar cells was decreased by Y-27632, and migration of macrophages, neutrophils, and fibroblasts in vitro was inhibited by Y-27632 regardless of various stimuli. Although expression of ROCK-II mRNA in the lung homogenates of the BLM-treated mice was increased approximately 9-fold, expression of ROCK-II protein showed only a slight tendency to increase. BLM elevated MLC phosphorylationlevels, and Y-27632 inhibited BLM response. These findings indicate that the Rho/ROCK-mediated pathway plays an important role in IPF, and that blocking of this pathway leads to inhibition of IPF development.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 15:38:33