Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8259686 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2015 | 9 Pages |
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease of unknown cause that typically leads to respiratory failure and death within 3-5 years 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+/âcapns1flox/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.
Keywords
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Authors
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,