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Int J Mol Sci. 2012;13(7):8293-307. doi: 10.3390/ijms13078293. Epub 2012 Jul 4.

Fasudil, a Rho-kinase inhibitor, attenuates bleomycin-induced pulmonary fibrosis in mice.

Author information

1
Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; E-Mails: jiang.cg@hotmail.com (C.J.); pumchhh@126.com (H.H.); liujiafree@163.com (J.L.); wangyanxun2008@163.com (Y.W.).

Abstract

The mechanisms underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF) involve multiple pathways, such as inflammation, epithelial mesenchymal transition, coagulation, oxidative stress, and developmental processes. The small GTPase, RhoA, and its target protein, Rho-kinase (ROCK), may interact with other signaling pathways known to contribute to pulmonary fibrosis. This study aimed to determine the beneficial effects and mechanisms of fasudil, a selective ROCK inhibitor, on bleomycin-induced pulmonary fibrosis in mice. Our results showed that the Aschcroft score and hydroxyproline content of the bleomycin-treated mouse lung decreased in response to fasudil treatment. The number of infiltrated inflammatory cells in the bronchoalveolar lavage fluid (BALF) was attenuated by fasudil. In addition, fasudil reduced the production of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), alpha-smooth muscle actin (α-SMA), and plasminogen activator inhibitor-1 (PAI-1) mRNA and protein expression in bleomycin-induced pulmonary fibrosis. These findings suggest that fasudil may be a potential therapeutic candidate for the treatment of pulmonary fibrosis.

KEYWORDS:

connective tissue growth factor; fasudil; plasminogen activator inhibitor-1; pulmonary fibrosis; transforming growth factor-β1

PMID:
22942703
PMCID:
PMC3430234
DOI:
10.3390/ijms13078293
[Indexed for MEDLINE]
Free PMC Article

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