miRNA-200a对人主动脉内皮细胞间质转化的影响及其机制

doi:10.3969/j.issn.1671-7171.2017.09.008

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Abstract 【Objective】To investigate the effect and the underlying mechanism of miRNA(miR)-200a in regulating TGF-β1-induced endothelial-mesenchymal transition (EndMT) of human aortic endothelial cells (HAVC) by targeting inhibition of high-mobility group protein box1, (HMGB1) .【Methods】1. The expression of miR-200a in human aortic endothelial cell lysates (HAEC) was detected under different concentrations of TGF-β1. 2. The expressions of platelet endothelial cell adhesion molecule-1 (CD31), endothelium-cadherin (VE-cadherin), fibroblast-specific protein-1 (FSP-1) andα-smooth muscle actin (α-SMA) were determined after miR-200a mimics/mimic NC transfection occurred in HAEC with or without TGF-β1 treatment. 3. The expression levels of HMGB1 in miRNA-200a mimics/mimic NC-transfected HAECs that were and were not treated with TGF-β1 were determined. 4. The binding relationship between miR-200a and HMGB1 3'UTR was detected by luciferase assay. 5. The protein expressions of CD31, VE-cadherin, FSP-1 and α-SMA in HAEC transfected with miR-200a mimics and HMGB1 alone or in combination were detected.【Results】1. TGF-β1 inhibited the expression of miR-200a(P＜0.01). 2. miR-200a inhibited TGF-β1-induced EndMT, up-regulated CD31(P＜0.01) and VE-cadherin(P＜0.001), while down- regulating FSP-1 (P＜0.001) and α-SMA (P＜0.01) expression. 3. miR-200a inhibited the expression of HMGB1(P＜0.001), while TGF- β1 promoted the expression of HMGB1(P＜0.001). 4. miR-200a binded to the 3'UTR region of HMGB1. 5. HMGB1 attenuated miR-200a inhibition of EndMT and down-regulated the expression of CD31(P＜0.01) and VE-cadherin(P＜0.01), while up-regulated the expression of α-SMA(P＜0.01) and FSP-1(P＜0.001).【Conclusion】The transfection of HMGB1 plasmid promoted the EndMT process of human aortic endothelial cell.The transfection of miR-200a inhibited the expression of HMGB1 and inhibited EndMT of human aortic endothelial cell induced by TGF-β1.Therefore miRNA(miR)-200a targets the inhibition of high-mobility group protein box1, (HMGB1) in regulating TGF-β1-induced endothelial-mesenchymal transition.

Key words： MicroRNAs Aorta Endothelial Cells/CY Biotransformation Transforming Growth Factor beta1 High Mobility Group Proteins

Received: 22 May 2017

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R543.1

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	XIONG Ying
	SUN Yan
	LI Ying
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XIONG Ying,SUN Yan,LI Ying, et al. Effect and the Underlying Mechanism of miRNA-200a in Regulating TGF-β1-induced Endothelial-mesenchymal Transition of Human Aortic Endothelial Cells[J]. JOURNAL OF CLINICAL RESEARCH, 2017, 34(9): 1691-1696.

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http://www.jcr.net.cn/EN/10.3969/j.issn.1671-7171.2017.09.008 OR http://www.jcr.net.cn/EN/Y2017/V34/I9/1691

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