{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T22:15:59Z","timestamp":1768256159582,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T00:00:00Z","timestamp":1474934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Excessive proliferation of cardiac fibroblasts (CFs) and their transdifferentiation into myofibroblasts leads to expression of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA), as well as excessive synthesis and secretion of collagens. This process represents an important pathological basis for myocardial fibrosis (MF). MicroRNA (miR)\u2010154 and the Wnt signaling pathway play key roles in the above process, although their specific interactions are poorly understood. After transfecting CFs with miR\u2010154 mimics or inhibitors, miR\u2010154 was found to inhibit the expression of Dickkopf\u2010related protein 2 (DKK2), while miR\u2010154 inhibitors upregulated DKK2 expression in a Western blot analysis. In a subsequent dual\u2010luciferase activity assay, direct binding of miR\u2010154 to <jats:italic>DKK2<\/jats:italic> was detected. Further experiments demonstrated that transfection of <jats:italic>DKK2<\/jats:italic> siRNA or miR\u2010154 resulted in increased levels of \u03b2\u2010catenin, \u03b1\u2010SMA, and collagens I and III. Moreover, these changes were observed in association with increases in CF proliferation and migration, and reduced apoptosis. Conversely, transfection of miR\u2010154 inhibitors or DKK2 overexpression vector resulted in lower expression levels of \u03b2\u2010catenin, \u03b1\u2010SMA, and collagens I and III, suppressed cell proliferation and migration, and enhanced apoptosis. Furthermore, in each assay, when the DKK2 overexpression vector and miR\u2010154 mimics were co\u2010transfected, the functions of each component were counteracted by the other. Therefore, in CFs, targeting of <jats:italic>DKK2<\/jats:italic> by miR\u2010154 leads to upregulation of \u03b2\u2010catenin expression and activation of the classical Wnt signaling pathway and CFs. These results suggest new targets for the clinical treatment of MF and ischemic heart disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cbin.10655","type":"journal-article","created":{"date-parts":[[2016,8,20]],"date-time":"2016-08-20T09:42:39Z","timestamp":1471686159000},"page":"1271-1279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["MiR\u2010154 directly suppresses <i>DKK2<\/i> to activate Wnt signaling pathway and enhance activation of cardiac fibroblasts"],"prefix":"10.1002","volume":"40","author":[{"given":"Li\u2010Ye","family":"Sun","sequence":"first","affiliation":[{"name":"Shandong University School of Medicine Jinan 250012 Shandong China"},{"name":"Department of Geratology Yantai Yuhuangding Hospital Yantai 264000 Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi\u2010Dong","family":"Bie","sequence":"additional","affiliation":[{"name":"Shandong University School of 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