Advanced Glycation End Products Activate the miRNA/RhoA/ROCK2 Pathway in Endothelial Cells. (February 2014)

• Record Type: Journal Article
• Authors: Wu, Xiao‐dan; Liu, Wei‐lin; Zeng, Kai; Lei, Hong‐yi; Zhang, Qing‐guo; Zhou, Shu‐qin; Xu, Shi‐yuan
• Is Part Of: Microcirculation. Volume 21:Number 2(2014:Feb.)
• Page Start: 178
• Page End: 186
• Publication Date: 2014-02
• Subjects: Biological transport -- Periodicals; Microcirculation -- Physiology -- Periodicals; 612.135
• DOI: 10.1111/micc.12104
• Languages: English
• ISSNs: 1073-9688

Abstract

<abstract abstract-type="main" id="micc12104-abs-0001"> <title>Abstract</title> <sec id="micc12104-sec-0001" sec-type="section"> <title>Objective</title> <p>AGEs induce endothelial cell dysfunction in HUVECs, resulting in ROS production and triggering apoptosis. This study sought to identify miRNAs involved in AGE‐induced endothelial cell injury.</p> </sec> <sec id="micc12104-sec-0002" sec-type="section"> <title>Methods</title> <p>Microarray analysis to identify miRNAs altered with AGE stimulation was undertaken, and results were confirmed using real‐time quantitative polymerase chain reaction. The interaction of miRNAs with the <italic>RhoA</italic> and <italic>ROCK2</italic> genes was confirmed using luciferase assays, and their effects on expression were determined using Western blot analysis. The effects of AGEs and miRNAs on endothelial cell permeability were assessed.</p> </sec> <sec id="micc12104-sec-0003" sec-type="section"> <title>Results</title> <p>AGEs induced ROS production and apoptosis of HUVECs (<italic>p </italic><<italic> </italic>0.05). AGE‐induced miR‐200b and miR‐200c downregulation led to increased expression of their target genes, <italic>RhoA</italic> and <italic>ROCK</italic>, respectively. AGE‐induced endothelial cell permeability and F‐actin expression were significantly reduced with both miR‐200b and miR‐200c mimics (<italic>p </italic><<italic> </italic>0.05). Furthermore, AGE‐induced stress fiber formation was reduced in cells treated with miR‐200b mimics.</p> </sec> <sec id="micc12104-sec-0004" sec-type="section"> <title>Conclusion</title> <p>miR‐200b and miR‐200c are suppressed in AGE‐induced endothelial cell injury, resulting in unregulated RhoA/ROCK2 signaling. Further studies are necessary to evaluate the therapeutic value of targeting miRNAs or their target genes for treatment of vascular diseases.</p> </sec> </abstract>