國家衛生研究院 NHRI:Item 3990099045/10307
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10307


    Title: MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases
    Authors: Lee, DY;Lin, TE;Lee, CI;Zhou, J;Huang, YH;Lee, PL;Shih, YT;Chien, S;Chiu, JJ
    Contributors: Institute of Cellular and Systems Medicine
    Abstract: Histone deacetylases (HDACs) and microRNAs (miRs) have emerged as two important epigenetic factors in the regulation of vascular physiology. This study aimed to elucidate the relationship between HDACs and miRs in the hemodynamic modulation of endothelial cell (EC) dysfunction. We found that miR-10a has the lowest expression among all examined shear-responsive miRs in ECs under oscillatory shear stress (OS), and a relatively high expression under pulsatile shear stress (PS). PS and OS alter EC miR-10a expression to regulate the expression of its direct target GATA6 and downstream vascular cell adhesion molecule (VCAM)-1. PS induces the expression, nuclear accumulation, and association of retinoid acid receptor-alpha (RARalpha) and retinoid X receptor-alpha (RXRalpha). RARalpha and RXRalpha serve as a "director" and an "enhancer," respectively, to enhance RARalpha binding to RA-responsive element (RARE) and hence miR-10a expression, thus down-regulating GATA6/VCAM-1 signaling in ECs. In contrast, OS induces associations of "repressors" HDAC-3/5/7 with RARalpha to inhibit the RARalpha-directed miR-10a signaling. The flow-mediated miR-10a expression is regulated by Kruppel-like factor 2 through modulation in RARalpha-RARE binding, with the consequent regulation in GATA6/VCAM-1 in ECs. These results are confirmed in vivo by en face staining on the aortic arch vs. the straight thoracic aorta of rats. Our findings identify a mechanism by which HDACs and RXRalpha modulate the hormone receptor RARalpha to switch miR-10a expression and hence the proinflammatory vs. anti-inflammatory responses of vascular endothelium under different hemodynamic forces.
    Date: 2017-02-21
    Relation: Proceedings of the National Academy of Sciences of the United States of America. 2017 Feb 21;114(8):2072-2077.
    Link to: http://dx.doi.org/10.1073/pnas.1621425114
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0027-8424&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000395099500094
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85013272350
    Appears in Collections:[Jeng-Jiann Chiu ] Periodical Articles

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