Activation of calpain by renin-angiotensin system in pleural mesothelial cells mediates tuberculous pleural fibrosis

Jie Yang, Fei Xiang, Peng Cheng Cai, Yu Zhi Lu, Xiao Xiao Xu, Fan Yu, Feng Zhi Li, Peter A. Greer, Huan Zhong Shi, Qiong Zhou, Jian Bao Xin, Hong Ye, Yunchao Su, Wan Li Ma

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Pleural fibrosis is defined as an excessive deposition of extracellular matrix (ECM) components that results in destruction of the normal pleural tissue architecture. It can result from diverse inflammatory conditions, especially tuberculous pleurisy. Pleural mesothelial cells (PMCs) play a pivotal role in pleural fibrosis. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodeling. However, the role of calpain in pleural fibrosis remains unknown. In the present study, we found that tuberculous pleural effusion (TPE) induced calpain activation in PMCs and that inhibition of calpain prevented TPE-induced collagen-I synthesis and cell proliferation of PMCs. Moreover, our data revealed that the levels of angiotensin (ANG)-converting enzyme (ACE) were significantly higher in pleural fluid of patients with TPE than those with malignant pleural effusion, and ACE-ANG II in TPE resulted in activation of calpain and subsequent triggering of the phosphatidylinositol 3-kinase (PI3K)/Akt/NF-κB signaling pathway in PMCs. Finally, calpain activation in PMCs and collagen depositions were confirmed in pleural biopsy specimens from patients with tuberculous pleurisy. Together, these studies demonstrated that calpain is activated by renin-angiotensin system in pleural fibrosis and mediates TPE-induced collagen-I synthesis and proliferation of PMCs via the PI3K/Akt/NF-κB signaling pathway. Calpain in PMCs might be a novel target for intervention in tuberculous pleural fibrosis.

Original languageEnglish (US)
Pages (from-to)L145-L153
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume311
Issue number1
DOIs
StatePublished - Jul 1 2016

Keywords

  • Calpain
  • Fibrosis
  • Pleural effusion
  • Pleural mesothelial cell
  • Tuberculosis

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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