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全反式维甲酸在平滑肌细胞中上调apelin基因表达的分子机制

吕心瑞, 王葆辉, 陈明亮, 徐晓, 王保芳

河南大学医学院生理教研室，开封 475004；开封市儿童医院神经内科，开封 475004

摘要

本文旨在研究全反式维甲酸(all-trans retinoic acid, ATRA)在血管平滑肌细胞(vascular smooth muscle cell, VSMC)中对apelin基因表达的影响及分子机制。我们用RT-PCR、实时定量PCR和免疫印迹分析检测ATRA对VSMC中apelin基因表达的影响，然后在VSMC中用小干扰RNA转染下调内源性维甲酸受体α (retinoic acid receptor α, RARα)或用腺病毒载体过表达RARα后，检测ATRA对apelin基因表达的影响。结果显示ATRA能以时间和浓度依赖的方式诱导apelin基因的表达，同时RARα表达水平也显著升高，但RARβ和RARγ表达水平无显著变化。利用小干扰RNA下调内源性RARα或用RARα选择性抑制剂Ro 41-5253抑制RARα活性后，再用ATRA刺激VSMC，ATRA对apelin基因表达的诱导作用受到显著抑制，而过表达RARα，则可促进apelin的表达升高。以上结果表明，ATRA可以上调VSMC中apelin基因表达水平，其分子机制是通过其核受体RARα介导完成的。

关键词： 全反式维甲酸; apelin基因; 血管平滑肌细胞

分类号：R34

[Role and mechanism of all-trans retinoic acid in up-regulating apelin expression in vascular smooth muscle cells.] [Article in Chinese]

LV Xin-Rui, WANG Bao-Hui, CHEN Ming-Liang, XU Xiao, WANG Bao-Fang

Department of Physiology, Medical College of Henan University, Kaifeng 475004, China； Department of Neurology, Kaifeng Children’s Hospital, Kaifeng 475004, China

Abstract

This study was aimed to investigate the mechanism of all-trans retinoic acid (ATRA) up-regulating apelin expression in vascular smooth muscle cells (VSMCs). The effect of ATRA on apelin expression in the VSMCs was investigated by RT-PCR, real-time PCR and Western blot analysis. To further define whether retinoic acid receptor α (RARα) mediated the induction of apelin by ATRA, endogenous RARα was down regulated by transfection of siRNA against RARα (si-RARα) or RARα was over-expressed by infection of the adenovirus vector pAd-GFP-RARα in the VSMCs. The results showed that ATRA significantly induced apelin expression in a time- and dose-dependent manner in the VSMCs. Although RARα expression was increased in a time-dependent manner, the expressions of RARβ and RARγ were little changed by the ATRA treatment. When VSMCs were treated with a RARα antagonist Ro 41-5253 prior to the addition of ATRA, or si-RARα was used to down regulate endogenous RARα expression, the blockade of RARα signaling partially reduced the response of apelin to ATRA. Moreover, RARα over-expression, induced by infection of pAd-GFP-RARα, further increased the induction of apelin by ATRA. In conclusion, ATRA may up-regulate apelin expression in VSMCs, and the mechanism may be RARα dependent.

Key words: all-trans retinoic acid; apelin; vascular smooth muscle cells

收稿日期：2014-11-02　　录用日期：2014-12-16

通讯作者：王保芳　　E-mail: wbfyky@tom.com

引用本文：

吕心瑞, 王葆辉, 陈明亮, 徐晓, 王保芳. 全反式维甲酸在平滑肌细胞中上调apelin基因表达的分子机制[J]. 生理学报 2015; 67 (2): 186-192.

LV Xin-Rui, WANG Bao-Hui, CHEN Ming-Liang, XU Xiao, WANG Bao-Fang. [Role and mechanism of all-trans retinoic acid in up-regulating apelin expression in vascular smooth muscle cells.] [Article in Chinese]. Acta Physiol Sin 2015; 67 (2): 186-192 (in Chinese with English abstract).