| First Author | Mishra R | Year | 2007 |
| Journal | Am J Physiol Cell Physiol | Volume | 292 |
| Issue | 4 | Pages | C1361-9 |
| PubMed ID | 17135298 | Mgi Jnum | J:135915 |
| Mgi Id | MGI:3794798 | Doi | 10.1152/ajpcell.00370.2006 |
| Citation | Mishra R, et al. (2007) TGF-beta-regulated collagen type I accumulation: role of Src-based signals. Am J Physiol Cell Physiol 292(4):C1361-9 |
| abstractText | Transforming growth factor-beta (TGF-beta) stimulates myofibroblast transdifferentiation, leading to type I collagen accumulation and fibrosis. We investigated the function of Src in TGF-beta-induced collagen I accumulation. In human mesangial cells, PTyr416 Src (activated Src) was 3.3-fold higher in TGF-beta-treated cells than in controls. Src activation by TGF-beta was blocked by rottlerin and by a dominant negative mutant of protein kinase Cdelta (PKCdelta), showing that TGF-beta activates Src by a PKCdelta-based mechanism. Pharmacological inhibitors and a dominant negative Src mutant prevented the increase in collagen type I secretion in cells exposed to TGF-beta. Similarly, on-target Src small interference RNA (siRNA) prevented type I collagen secretion in response to TGF-beta, but off-target siRNA complexes had no effect. It is well established in mesangial cells that upregulation of type I collagen by TGF-beta requires extracellular signal-regulated kinase 1/2 (ERK1/2), and we found that activation of ERK1/2 by TGF-beta requires Src. In conclusion, these results suggest that stimulation of collagen type I secretion by TGF-beta requires a PKCdelta-Src-ERK1/2 signaling motif. |
