| First Author | Gu J | Year | 2012 |
| Journal | Exp Cell Res | Volume | 318 |
| Issue | 16 | Pages | 2105-15 |
| PubMed ID | 22749815 | Mgi Jnum | J:187176 |
| Mgi Id | MGI:5435637 | Doi | 10.1016/j.yexcr.2012.06.015 |
| Citation | Gu J, et al. (2012) Angiotensin II increases CTGF expression via MAPKs/TGF-beta1/TRAF6 pathway in atrial fibroblasts. Exp Cell Res 318(16):2105-15 |
| abstractText | The activation of transforming growth factor-beta1(TGF-beta1)/Smad signaling pathway and increased expression of connective tissue growth factor (CTGF) induced by angiotensin II (AngII) have been proposed as a mechanism for atrial fibrosis. However, whether TGFbeta1/non-Smad signaling pathways involved in AngII-induced fibrogenetic factor expression remained unknown. Recently tumor necrosis factor receptor associated factor 6 (TRAF6)/TGFbeta-associated kinase 1 (TAK1) has been shown to be crucial for the activation of TGF-beta1/non-Smad signaling pathways. In the present study, we explored the role of TGF-beta1/TRAF6 pathway in AngII-induced CTGF expression in cultured adult atrial fibroblasts. AngII (1muM) provoked the activation of P38 mitogen activated protein kinase (P38 MAPK), extracellular signal-regulated kinase 1/2(ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). AngII (1muM) also promoted TGFbeta1, TRAF6, CTGF expression and TAK1 phosphorylation, which were suppressed by angiotensin type I receptor antagonist (Losartan) as well as p38 MAPK inhibitor (SB202190), ERK1/2 inhibitor (PD98059) and JNK inhibitor (SP600125). Meanwhile, both TGFbeta1 antibody and TRAF6 siRNA decreased the stimulatory effect of AngII on TRAF6, CTGF expression and TAK1 phosphorylation, which also attenuated AngII-induced atrial fibroblasts proliferation. In summary, the MAPKs/TGFbeta1/TRAF6 pathway is an important signaling pathway in AngII-induced CTGF expression, and inhibition of TRAF6 may therefore represent a new target for reversing Ang II-induced atrial fibrosis. |
