{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:53:32Z","timestamp":1768902812757,"version":"3.49.0"},"reference-count":0,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Physiol Biochem"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1159\/000485356","type":"journal-article","created":{"date-parts":[[2017,11,24]],"date-time":"2017-11-24T22:01:19Z","timestamp":1511560879000},"page":"884-896","source":"Crossref","is-referenced-by-count":31,"title":["Downregulated MicroRNA-195 in the Bicuspid Aortic Valve Promotes Calcification of Valve Interstitial Cells via Targeting SMAD7"],"prefix":"10.1159","volume":"44","author":[{"given":"Junjie","family":"Du","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keshuai","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongfeng","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2017,11,24]]},"container-title":["Cellular Physiology and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/485356","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/485356","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:24:03Z","timestamp":1745425443000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000485356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":0,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,12,18]]}},"URL":"https:\/\/doi.org\/10.1159\/000485356","archive":["Portico"],"relation":{},"ISSN":["1015-8987","1421-9778"],"issn-type":[{"value":"1015-8987","type":"print"},{"value":"1421-9778","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017]]}}}