Angiotensin II increases collagen I expression via transforming growth factor-beta1 and extracellular signal-regulated kinase in cardiac fibroblasts.
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.
Department of Cardiology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. xiurengao@yahoo.com
Xiuren
X
Gao
Xuyu
X
He
Bing
B
Luo
Longyun
L
Peng
Jun
J
Lin
Zhiyi
Z
Zuo
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
D024042:Collagen Type I; D044140:Receptor, Angiotensin, Type 1; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D048049:Extracellular Signal-Regulated MAP Kinases