Crosstalk between calpain activation and TGF-β1 augments collagen-I synthesis in pulmonary fibrosis

Feng Zhi Li, Peng Cheng Cai, Lin Jie Song, Li Ling Zhou, Qian Zhang, Shan Shan Rao, Yu Xia, Fei Xiang, Jian Bao Xin, Peter A. Greer, Huan Zhong Shi, Yunchao Su, Wan Li Ma, Hong Ye

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease of unknown cause that typically leads to respiratory failure and death within 3-5years of diagnosis. TGF-β1 is considered a major profibrotic factor. However, TGF-β1 is necessary but not sufficient to the pathogenesis of fibrotic lesion of the lungs. Recent observations have revealed that calpain, a calcium dependent protease, plays a pivotal role in tissue remodeling and fibrosis. However, the mechanism of calpain mediating pulmonary fibrosis is not understood. Calpain conditional knockout (ER-Cre+/-capns1flox/flox) mice and primary human lung fibroblasts (HLFs) were used here to investigate the relationship between calpain and TGF-β1. Calpain knockout mice were protected from fibrotic effects of bleomycin. Bleomycin induced increases in TGF-β1 via calpain activation in HLFs. Moreover, TGF-β1 also activated calpain. This crosstalk between calpain activation and TGF-β1 triggered the downstream signaling pathway including TGF-β1 Smad2/3 and non-Smad (Akt) pathways, as well as collagen-I synthesis. Taken together, our data indicate that the crosstalk between calpain activation and TGF-β1 augments collagen-I synthesis in HLFs and in pulmonary fibrosis. Intervention in the crosstalk between calpain activation and TGF-β1 is a novel potential strategy to prevent pulmonary fibrosis.

Original languageEnglish (US)
Pages (from-to)1796-1804
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1852
Issue number9
DOIs
StatePublished - Sep 1 2015

Keywords

  • Calpain
  • Collagen
  • Fibroblasts
  • Pulmonary fibrosis
  • Smad
  • TGF-β1

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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  • Cite this

    Li, F. Z., Cai, P. C., Song, L. J., Zhou, L. L., Zhang, Q., Rao, S. S., Xia, Y., Xiang, F., Xin, J. B., Greer, P. A., Shi, H. Z., Su, Y., Ma, W. L., & Ye, H. (2015). Crosstalk between calpain activation and TGF-β1 augments collagen-I synthesis in pulmonary fibrosis. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1852(9), 1796-1804. https://doi.org/10.1016/j.bbadis.2015.06.008