Role of eukaryotic translation initiation factors 3a in hypoxia-induced right ventricular remodeling of rats

Nov 28, 2015Life sciences

Role of Protein-Making Factors in Low Oxygen–Related Changes in the Right Heart of Rats

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Abstract

The expression of eIF3a increased significantly in the right ventricle of remodeling rats.

Right ventricular remodeling was induced by hypoxia in rats over a three-week period.
Increased levels of eIF3a were associated with higher expression of α-SMA and collagen in the right ventricle.
TGF-β1 promoted the proliferation and differentiation of cardiac fibroblasts while also increasing eIF3a levels and decreasing p27 levels.
Knockdown of eIF3a using siRNA inhibited TGF-β1-induced proliferation and the up-regulation of α-SMA and collagen in cardiac fibroblasts.
The negative impact of eIF3a siRNA on TGF-β1 was linked to the reversal of p27 down-regulation.

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AIM: Eukaryotic translation initiation factors 3a (eIF3a) is involved in regulating cell cycle, cell division, growth and differentiation. Previous studies suggest a role of eIF3a on fibrosis disease and cellular proliferation and differentiation of fibroblasts. The present study aims to investigate the role of eIF3a on hypoxia-induced right ventricular (RV) remodeling and underlying mechanism.

MAIN METHODS: RV remodeling was induced by hypoxia (10% O2, 3 weeks) in rats. Primary cardiac fibroblasts were cultured in vitro and their proliferation was investigated by MTS and EdU incorporation method. eIF3a knockdown was conducted by eIF3a siRNA. The expression/level of TGF-β1, eIF3a, p27 and α-SMA, collagen-I, collagen-III, ANP and BNP were analyzed by ELISA, real-time PCR or Western blot.

KEY FINDINGS: The expression of eIF3a was obviously increased in right ventricle of RV remodeling rats accompanied by up-regulation of α-SMA and collagens. In cultured cardiac fibroblasts, application of exogenous TGF-β1-induced cellular proliferation and differentiation concomitantly with up-regulation of eIF3a expression and down-regulation of p27 expression. The effects of TGF-β1-induced proliferation and up-regulation of α-SMA and collagen in cardiac fibroblasts were abolished by eIF3a siRNA. eIF3a siRNA reversed TGF-β1 induced down-regulation of p27 expression.

SIGNIFICANCE: The eIF3a plays a crucial role in hypoxia-induced RV remodeling by regulating TGF-β1-induced proliferation and differentiation of cardiac fibroblasts, which is mediated via eIF3a/p27 pathway.

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Role of eukaryotic translation initiation factors 3a in hypoxia-induced right ventricular remodeling of rats

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