期刊
BMC MOLECULAR BIOLOGY
卷 20, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12867-019-0125-z
关键词
Myocyte enhancer factor 2A; Human coronary artery endothelial cells; Vascular endothelial dysfunction; Senescence; Cardiovascular disease; PIK3CG
资金
- Department of Education of Guangdong Province [2014KTSCX098]
- Guangdong Provincial Science and Technology plan project [2016A020215142]
- General Programs of the National Natural Science Foundation of China [81370463, 81570259]
Background: Myocyte enhancer factor 2A (MEF2A) plays an important role in cell proliferation, differentiation and survival. Functional deletion or mutation in MEF2A predisposes individuals to cardiovascular disease mainly caused by vascular endothelial dysfunction. However, the effect of the inhibition of MEF2A expression on human coronary artery endothelial cells (HCAECs) is unclear. In this study, expression of MEF2A was inhibited by specific small interference RNA (siRNA), and changes in mRNA profiles in response to MEF2A knockdown were analyzed using an Agilent human mRNA array. Results: Silencing of MEF2A in HCAECs accelerated cell senescence and suppressed cell proliferation. Microarray analysis identified 962 differentially expressed genes (DEGs) between the MEF2A knockdown group and the negative control group. Annotation clustering analysis showed that the DEGs were preferentially enriched in gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to proliferation, development, survival, and inflammation. Furthermore, 61 of the 578 downregulated DEGs have at least one potential MEF2A binding site in the proximal promoter and were mostly enriched in the GO terms reproduction and cardiovascular. The protein-protein interaction network analyzed for the downregulated DEGs and the DEGs in the GO terms Cardiovascular and aging revealed that PIK3CG, IL1B, IL8, and PRKCB were included in hot nodes, and the regulation of the longevity-associated gene PIK3CG by MEF2A has been verified at the protein level, suggesting that PIK3CG might play a key role in MEF2A knockdown induced HCAEC senescence. Conclusions: MEF2A knockdown accelerates HCAEC senescence, and the underlying molecular mechanism may be involved in down-regulation of the genes related with cell proliferation, development, inflammation and survival, in which PIK3CG may play a key role.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据