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Angiotensin II increases periostin expression via Ras/p38 MAPK/CREB and ERK1/2/TGF-{beta}1 pathways in cardiac fibroblasts.

Authors: Li, L  Fan, D  Wang, C  Wang, JY  Cui, XB  Wu, D  Zhou, Y  Wu, LL 
Citation: Li L, etal., Cardiovasc Res. 2011 Mar 2.
Pubmed: (View Article at PubMed) PMID:21367774
DOI: Full-text: DOI:10.1093/cvr/cvr067

Aims Angiotensin II (AngII) is involved in extracellular matrix (ECM) accumulation contributing to heart failure. Periostin, a 90-kDa ECM protein, is a key regulator of cardiac fibrosis, and its expression is significantly higher in failing hearts. We determined the modulatory effect of AngII on periostin level and explored the possible signal transduction mechanism. Methods and Results AngII (400 ng/kg/min) or normal saline was infused subcutaneously for 28 days into rats; AngII antagonism was with losartan (10 mg/kg/day orally). AngII infusion induced cardiac fibrosis and increased periostin expression, which was attenuated by losartan. In cultured adult rat cardiac fibroblasts, AngII promoted the mRNA and protein expression of periostin. AngII provoked activation of cAMP response element-binding protein (CREB), and CREB small interfering RNA (siRNA) suppressed AngII-induced periostin expression. Inhibition of p38 mitogen-activated protein kinase (p38 MAPK) with SB202190 attenuated AngII-induced CREB activation and periostin expression. Transfection with RasGRP1 siRNA or RasN17 dominant-negative plasmid prevented AngII-induced p38 MAPK phosphorylation and periostin expression. Transforming growth factor (TGF)-beta1 antibody decreased the stimulatory effect of AngII on periostin expression. The extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 attenuated AngII-induced TGF-beta1 expression, Smad2/3 nuclear accumulation, and periostin expression. Conclusion The activation of the Ras/p38 MAPK/CREB pathway is required for AngII-induced periostin expression. ERK1/2 also participates in AngII-induced periostin expression by regulating TGF-beta1/Smad signaling.


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CRRD Object Information
CRRD ID: 5129174
Created: 2011-03-25
Species: All species
Last Modified: 2011-03-25
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.