Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation

被引：26

作者：

Jiang, Xue-Yan ^{[1
,2
]}

Feng, Yu-Liang ^{[1
,3
]}

Ye, Li-Tong ^{[1
]}

Li, Xiao-Hong ^{[1
]}

Feng, Juan ^{[1
]}

Zhang, Meng-Zhen ^{[1
]}

Shelat, Harnath S. ^{[2
]}

Wassler, Michael ^{[2
]}

Li, Yangxin ^{[2
]}

Geng, Yong-Jian ^{[2
]}

Yu, Xi-Yong ^{[1
,3
]}

机构：

[1] Southern Med Univ, Guangdong Acad Med Sci, Guangdong Cardiovasc Inst Guangdong Gen Hosp, Guangzhou 510080, Peoples R China

[2] Univ Texas McGovern Sch Med, Texas Heart Inst, Ctr Cardiovascular Biol & Atherosclerosis Res, Houston, TX 77030 USA

[3] Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Clin Pharmacol, Guangzhou 511436, Peoples R China

来源：

STEM CELL REPORTS | 2017年 / 8卷 / 02期

基金：

中国国家自然科学基金;

关键词：

CONGENITAL HEART-DEFECTS; EMBRYONIC STEM-CELLS; MATERNAL SMOKING; ACETYLCHOLINE-RECEPTOR; EPIGENETIC REGULATION; PROMOTER METHYLATION; F2RL3; METHYLATION; BLOOD-PRESSURE; LUNG-CANCER; EXPOSURE;

D O I：

10.1016/j.stemcr.2016.12.016

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Maternal nicotine exposure causes alteration of gene expression and cardiovascular programming. The discovery of nicotine-medicated regulation in cardiogenesis is of major importance for the study of cardiac defects. The present study investigated the effect of nicotine on cardiac gene expression and epigenetic regulation during myocardial differentiation. Persistent nicotine exposure selectively inhibited expression of two cardiac genes, Tbx5 and Gata4, by promoter DNA hypermethylation. The nicotine-induced suppression on cardiac differentiation was restored by general nicotinic acetylcholine receptor inhibition. Consistent results of Tbx5 and Gata4 gene suppression and cardiac function impairment with decreased left ventricular ejection fraction were obtained from in vivo studies in offspring. Our results present a direct repressive effect of nicotine on myocardial differentiation by regulating cardiac gene suppression via promoter DNA hypermethylation, contributing to the etiology of smoking-associated cardiac defects.

引用

页码：290 / 304

页数：15

共 45 条

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