| First Author | Davis J | Year | 2012 |
| Journal | Dev Cell | Volume | 23 |
| Issue | 4 | Pages | 705-15 |
| PubMed ID | 23022034 | Mgi Jnum | J:189077 |
| Mgi Id | MGI:5444322 | Doi | 10.1016/j.devcel.2012.08.017 |
| Citation | Davis J, et al. (2012) A TRPC6-Dependent Pathway for Myofibroblast Transdifferentiation and Wound Healing In Vivo. Dev Cell 23(4):705-15 |
| abstractText | After injury or cytokine stimulation, fibroblasts transdifferentiate into myofibroblasts, contractile cells that secrete extracellular matrix for wound healing and tissue remodeling. Here, a genome-wide screen identified TRPC6, a Ca(2+) channel necessary and sufficient for myofibroblast transformation. TRPC6 overexpression fully activated myofibroblast transformation, while fibroblasts lacking Trpc6 were refractory to transforming growth factor beta (TGF-beta) and angiotensin II-induced transdifferentiation. Trpc6 gene-deleted mice showed impaired dermal and cardiac wound healing after injury. The profibrotic ligands TGF-beta and angiotensin II induced TRPC6 expression through p38 mitogen-activated protein kinase (MAPK) serum response factor (SRF) signaling via the TRPC6 promoter. Once induced, TRPC6 activates the Ca(2+)-responsive protein phosphatase calcineurin, which itself induced myofibroblast transdifferentiation. Moreover, inhibition of calcineurin prevented TRPC6-dependent transdifferentiation and dermal wound healing. These results demonstrate an obligate function for TRPC6 and calcineurin in promoting myofibroblast differentiation, suggesting a comprehensive pathway for myofibroblast formation in conjunction with TGF-beta, p38 MAPK, and SRF. |
