| First Author | Hofmann K | Year | 2017 |
| Journal | Biochim Biophys Acta | Volume | 1863 |
| Issue | 2 | Pages | 560-568 |
| PubMed ID | 27932059 | Mgi Jnum | J:254041 |
| Mgi Id | MGI:6104417 | Doi | 10.1016/j.bbadis.2016.12.002 |
| Citation | Hofmann K, et al. (2017) Classical transient receptor potential 6 (TRPC6) channels support myofibroblast differentiation and development of experimental pulmonary fibrosis. Biochim Biophys Acta 1863(2):560-568 |
| abstractText | Pulmonary fibrosis (PF) is a chronic progressive lung disease without effective medical treatment options leading to respiratory failure and death within 3-5years of diagnosis. The pathological process of PF is driven by aberrant wound-healing involving fibroblasts and myofibroblasts differentiated by secreted profibrotic transforming growth factor beta (TGF-beta1). Classical transient receptor potential 6 (TRPC6), a Na(+)- and Ca(2+)-permeable cation channel, is able to promote myofibroblast conversion of primary rat cardiac and human dermal fibroblasts and TRPC6-deficiency impaired wound healing after injury. To study a potential role of TRPC6 in the development of PF we analyzed lung function, gene and protein expression in wild-type (WT) and TRPC6-deficient (TRPC6-/-) lungs utilizing a bleomycin-induced PF-model. Fibrotic WT-mice showed a significant higher death rate while bleomycin-treated TRPC6-deficient mice were partly protected from fibrosis as a consequence of a lower production of collagen and an almost normal function of the respiratory system (reduced resistance and elastance compared to fibrotic WT-mice). On a molecular level TGF-beta1 induced TRPC6 up-regulation, increased Ca(2+) influx and nuclear NFAT localization in WT primary murine lung fibroblasts (PMLFs) resulting in higher stress fiber formation and accelerated contraction rates as compared to treated TRPC6-deficient fibroblasts. Therefore, we conclude that TRPC6 is an important determinant for TGF-beta1-induced myofibroblast differentiation during fibrosis and specific channel inhibitors might be beneficial in a future treatment of PF. |
