Inhibition of angiotensin II and calpain attenuates pleural fibrosis

Lin Jie Song, Fei Xiang, Hong Ye, Hai Huang, Jie Yang, Fan Yu, Liang Xiong, Juan Juan Xu, Peter A. Greer, Huan Zhong Shi, Jian Bao Xin, Yunchao Su, Wan Li Ma

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Pleural fibrosis is associated with various inflammatory processes such as tuberculous pleurisy and bacterial empyema. There is currently no ideal therapeutic to attenuate pleural fibrosis. Some pro-fibrogenic mediators induce fibrosis through inflammatory processes, suggesting that blockage of these mediators might prevent pleural fibrosis. The MeT-5A human pleural mesothelial cell line (PMC) was used in this study as an in vitro model of fibrosis; and intra-pleural injection of bleomycin with carbon particles was used as an in vivo mouse model of pleural fibrosis. Calpain knockout mice, calpain inhibitor (calpeptin), and angiotensin (Ang) II type 1 receptor (AT1R) antagonist (losartan) were evaluated in prevention of experimental pleural fibrosis. We found that bleomycin and carbon particles induced calpain activation in cultured PMCs. This in vitro response was associated with increased collagen-I synthesis, and was blocked by calpain inhibitor or AT1R antagonist. Calpain genetic or treatment with calpeptin or losartan prevented pleural fibrosis in a mouse model induced by bleomycin and carbon particles. Our findings indicate that Ang II signaling and calpain activation induce collagen-I synthesis and contribute to fibrotic alterations in pleural fibrosis. Inhibition of Ang II and calpain might therefore be a novel strategy in treatment of pleural fibrosis.

Original languageEnglish (US)
Pages (from-to)46-52
Number of pages7
JournalPulmonary Pharmacology and Therapeutics
Volume48
DOIs
StatePublished - Feb 2018

Keywords

  • Angiotensin II
  • Calpain
  • Fibrosis
  • Pleural mesothelial cell

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

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  • Cite this

    Song, L. J., Xiang, F., Ye, H., Huang, H., Yang, J., Yu, F., Xiong, L., Xu, J. J., Greer, P. A., Shi, H. Z., Xin, J. B., Su, Y., & Ma, W. L. (2018). Inhibition of angiotensin II and calpain attenuates pleural fibrosis. Pulmonary Pharmacology and Therapeutics, 48, 46-52. https://doi.org/10.1016/j.pupt.2017.10.012