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Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice
Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
Department of Respiratory Medicine, Yijishan Hospital of Wannan Medical College, Wuhu 241001, China
* Author to whom correspondence should be addressed.
Received: 21 May 2012; in revised form: 19 June 2012 / Accepted: 28 June 2012 / Published: 4 July 2012
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: pulmonary fibrosis; fasudil; transforming growth factor-β1; connective tissue growth factor; plasminogen activator inhibitor-1
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MDPI and ACS Style
Jiang, C.; Huang, H.; Liu, J.; Wang, Y.; Lu, Z.; Xu, Z. Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice. Int. J. Mol. Sci. 2012, 13, 8293-8307.
Jiang C, Huang H, Liu J, Wang Y, Lu Z, Xu Z. Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice. International Journal of Molecular Sciences. 2012; 13(7):8293-8307.
Jiang, Chunguo; Huang, Hui; Liu, Jia; Wang, Yanxun; Lu, Zhiwei; Xu, Zuojun. 2012. "Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice." Int. J. Mol. Sci. 13, no. 7: 8293-8307.