Crosstalk between calpain activation and TGF-β1 augments collagen-I synthesis in pulmonary fibrosis
| Autor: | Qian Zhang, Shan Shan Rao, Li Ling Zhou, Feng Zhi Li, Fei Xiang, Peter A. Greer, Yunchao Su, Huan-Zhong Shi, Yu Xia, Hong Ye, Lin Jie Song, Jian Bao Xin, Peng Cheng Cai, Wan-Li Ma |
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| Rok vydání: | 2015 |
| Předmět: |
Bleomycin
Pulmonary fibrosis 03 medical and health sciences chemistry.chemical_compound Idiopathic pulmonary fibrosis 0302 clinical medicine Fibrosis TGF-β1 Conditional gene knockout medicine Molecular Biology Protein kinase B Smad 030304 developmental biology 0303 health sciences biology Calpain business.industry Fibroblasts medicine.disease 3. Good health Crosstalk (biology) chemistry 030220 oncology & carcinogenesis Immunology biology.protein Cancer research Molecular Medicine Collagen business |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1852:1796-1804 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2015.06.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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