| First Author | Li FZ | Year | 2015 |
| Journal | Biochim Biophys Acta | Volume | 1852 |
| Issue | 9 | Pages | 1796-804 |
| PubMed ID | 26071646 | Mgi Jnum | J:233923 |
| Mgi Id | MGI:5788380 | Doi | 10.1016/j.bbadis.2015.06.008 |
| Citation | Li FZ, et al. (2015) Crosstalk between calpain activation and TGF-beta1 augments collagen-I synthesis in pulmonary fibrosis. Biochim Biophys Acta 1852(9):1796-804 |
| abstractText | 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-beta1 is considered a major profibrotic factor. However, TGF-beta1 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(+/-)capns1(flox/flox)) mice and primary human lung fibroblasts (HLFs) were used here to investigate the relationship between calpain and TGF-beta1. Calpain knockout mice were protected from fibrotic effects of bleomycin. Bleomycin induced increases in TGF-beta1 via calpain activation in HLFs. Moreover, TGF-beta1 also activated calpain. This crosstalk between calpain activation and TGF-beta1 triggered the downstream signaling pathway including TGF-beta1 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-beta1 augments collagen-I synthesis in HLFs and in pulmonary fibrosis. Intervention in the crosstalk between calpain activation and TGF-beta1 is a novel potential strategy to prevent pulmonary fibrosis. |
