内皮功能障碍
内皮干细胞
转录因子
分子生物学
非翻译区
染色质免疫沉淀
血管性血友病因子
内皮
生物
细胞生物学
信使核糖核酸
发起人
基因表达
基因
免疫学
生物化学
内分泌学
血小板
体外
作者
Yaxuan Ren,Jikang Shi,Sainan Liu,Wenfei Zhu,Aiyu Shao,Yichun Qiao,Yong Li,Yunkai Liu,Yi Cheng,Yawen Liu
标识
DOI:10.1097/hjh.0000000000003359
摘要
Dysfunction of endothelial cells links to microvascular rarefaction, reflecting the pathogenesis of hypertension. Our previous studies found that miR-3656 reduces nitric oxide generation and von Willebrand factor (vWF) cleavage, thereby retarding blood flow and potentially increasing blood pressure. In this paper, we investigated mechanism of transcription regulation contributing to miR-3656-damaged endothelial cells in hypertension.The effects of miR-3656 on function of endothelial cells were analyzed on the basis of proliferation, migration, tube formation, and apoptosis. The mRNA level and protein level of genes were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Dual-luciferase reporter assay was performed to confirm the binding between miR-3656 and 3' untranslated region (UTR) of transcription factor AP-2 gamma ( TFAP2C ). The binding between TFAP2C and the promoter region of Krüppel-like factor 10 ( KLF10 ) was confirmed by chromatin immunoprecipitation-qPCR assay.miR-3656 impaired the cell proliferation, migration, tube formation, and apoptosis of endothelial cells. miR-3656 inhibited the expression of TFAP2C by directly targeting 3'UTR of TFAP2C ; moreover, miR-3656-induced injury of endothelial cells was rescued by TFAP2C overexpression. Furthermore, downregulated TFAP2C decreased KLF10 expression by binding to KLF10 promoter region, and upregulated KLF10 reversed the effects of silencing TFAP2C on endothelial cells. These inhibitory processes led to interference of miR-3656 to KLF10-promoted function of endothelial cells.TFAP2C/KLF10 axis is involved in miR-3656-related dysfunction of endothelial cells in hypertension. The 3'UTR of TFAP2C and KLF10 promoter region are the hubs of the TFAP2C/KLF10 axis.
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