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首页> 外文期刊>Cellular Physiology and Biochemistry >Downregulated MicroRNA-195 in the Bicuspid Aortic Valve Promotes Calcification of Valve Interstitial Cells via Targeting SMAD7
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Downregulated MicroRNA-195 in the Bicuspid Aortic Valve Promotes Calcification of Valve Interstitial Cells via Targeting SMAD7

机译：二尖瓣主动脉瓣膜中的MicroRNA-195下调通过靶向SMAD7促进瓣膜间质细胞的钙化。

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>Background/Aims: Aortic stenosis caused by leaflet calcification in the bicuspid aortic valve (BAV) is more accelerative than that in the tricuspid aortic valve (TAV). MicroRNA-195 (miR-195) is downregulated more in stenotic than in insufficient BAVs, but its expression in BAVs compared with TAVs is unclear. We aimed to investigate the roles of miR-195 and its calcification-related target SMAD7 in stenotic BAVs compared with those in TAVs. Methods: Twenty-one stenotic BAV and 29 TAV samples were collected from surgical patients and examined for the expression of miR-195 and SMAD7 by RT-PCR. The samples were also assessed by western blotting and immunohistochemistry for the functional protein alteration associated with calcification. Dual-luciferase assay was performed to determine the putative target of miR-195 before the effects of miR-195 expression on osteogenic progression was demonstrated in cultured porcine valve interstitial cells (VICs). Results: Compared with TAV, the expression of miR-195 was remarkably lower in the BAV leaflet with higher expression of SMAD7, which was then validated as a direct target of miR-195. Their negative correlation was then confirmed in cultured VICs. Under an osteogenic environment, the cellular calcification was promoted in miR-195-repressed VICs expressing higher BMP-2 and Runx2 and higher activity of MMP-2 compared with the controls. Finally, higher MMP-2 and MMP-9 expression and more collagen distribution were observed in BAV than TAV samples. Conclusions: miR-195 is downregulated more in stenotic BAV than TAV in this study. The downregulation of miR-195 is associated with valvular calcification via targeting SMAD7, which promotes the remodeling of the extracellular matrix.
机译：> 背景/目的： 二尖瓣主动脉瓣（BAV）的小叶钙化引起的主动脉瓣狭窄比三尖瓣主动脉瓣（TAV）的主动脉瓣狭窄更加速。与不足的BAV相比，狭窄的MicroRNA-195（miR-195）的下调更多，但与TAV相比，其在BAV中的表达尚不清楚。我们旨在研究miR-195及其钙化相关靶标 SMAD7 在狭窄BAV中与在TAV中的作用。 方法： 从手术患者中收集21份狭窄BAV和29份TAV样品，并通过RT检查其miR-195和 SMAD7 的表达。 -PCR。还通过蛋白质印迹和免疫组织化学评估样品中与钙化相关的功能性蛋白改变。在培养的猪瓣膜间质细胞（VIC）中证明了miR-195表达对成骨过程的影响之前，需进行双重荧光素酶测定法以确定miR-195的假定靶标。 结果： 与TAV相比，BAV小叶中miR-195的表达显着降低，而 SMAD7 的表达则更高，随后进行了验证作为miR-195的直接目标。然后在培养的VIC中证实了它们的负相关性。在成骨环境下，与对照组相比，表达更高的BMP-2和Runx2以及更高的MMP-2活性的miR-195抑制的VIC促进了细胞钙化。最后，与TAV样品相比，在BAV中观察到更高的MMP-2和MMP-9表达以及更多的胶原分布。 结论： 在这项研究中，狭窄的BAV中的miR-195比TAV的下调更多。 miR-195的下调与通过靶向 SMAD7 的瓣膜钙化有关，这促进了细胞外基质的重塑。

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