| First Author | Guo F | Year | 2013 |
| Journal | J Invest Dermatol | Volume | 133 |
| Issue | 6 | Pages | 1646-54 |
| PubMed ID | 23340735 | Mgi Jnum | J:197953 |
| Mgi Id | MGI:5494934 | Doi | 10.1038/jid.2013.28 |
| Citation | Guo F, et al. (2013) TAK1 is required for dermal wound healing and homeostasis. J Invest Dermatol 133(6):1646-54 |
| abstractText | Dermal connective tissue is a supportive structure required for skin's barrier function; dysregulated dermal homeostasis results in chronic wounds and fibrotic diseases. The multifunctional cytokine transforming growth factor (TGF) beta promotes connective tissue deposition, repair, and fibrosis. TGF-beta acts through well-defined canonical pathways; however, the non-canonical pathways through which TGF-beta selectively promotes connective tissue deposition are unclear. In dermal fibroblasts, we show that inhibition of the non-canonical TGF-beta-activated kinase 1 (TAK1) selectively reduced the ability of TGF-beta to induce expression of a cohort of wound healing genes, such as collagens, CCN2, TGF-beta1, and IL-6. Fibroblast-specific TAK1-knockout mice showed impaired cutaneous tissue repair and decreased collagen deposition, alpha-smooth muscle actin and CCN2 expression, proliferating cell nuclear antigen staining, and c-Jun N-terminal kinase and p38, but not Smad3, phosphorylation. TAK1-deficient fibroblasts showed reduced cell proliferation, migration, cell attachment/spreading, and contraction of a floating collagen gel matrix. TAK1-deficient mice also showed progressively reduced skin thickness and collagen deposition. Thus, TAK1 is essential for connective tissue deposition in the dermis. |
