| pubmed-article:19374881 | pubmed:abstractText | Angiotensin II is a powerful mediator to induce cardiac remodeling and fibrosis. Transforming growth factor-beta1 (TGF-beta1) and extracellular signal-regulated kinase (ERK) have been implicated in the angiotensin II-induced cardiac fibrosis. However, the signaling pathways for this angiotensin II effect and the interaction between ERK and the TGF-beta1 signaling in this effect have not been well-illustrated. Cardiac fibroblasts were prepared from the ventricles of adult male Sprague-Dawley rats. They were treated with 1 microM angiotensin II in the presence or absence of losartan (angiotensin II AT(1) receptor antagonist), PD123319 (angiotensin II AT(2) receptor antagonist), an anti-TGF-beta1 antibody or PD98059 (ERK inhibitor). The cells were collected for Western blotting and reverse transcription-polymerase chain reaction. Angiotensin II caused a significant increase of the expression of TGF-beta(1), ERK1, phosphorylated-Smad2/3, Smad4 and collagen I. This increase was attenuated by losartan but was not affected by PD123319. An anti-TGF-beta(1) antibody and PD98059 diminished angiotensin II-induced Smad2/3 phosphorylation and the expression of Smad7 and collagen I. Our results suggest that angiotensin II induces collagen I expression through angiotensin II AT(1) receptor-TGF-beta(1)-Smads signaling pathway in cardiac fibroblasts. ERK, by regulating Smads signaling, also participated in the angiotensin II-induced collagen I expression. | lld:pubmed |
