{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:09:21Z","timestamp":1788260961690,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["1R01HD094380"],"award-info":[{"award-number":["1R01HD094380"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Uterine leiomyoma (UL) is the most common gynaecologic tumour, affecting an estimated 70 to 80% of women. Leiomyomas develop from the transformation of myometrial stem cells into leiomyoma stem (or tumour\u2010initiating) cells. These cells undergo self\u2010renewal and differentiation to mature cells, both are necessary for the maintenance of tumour stem cell niche and tumour growth, respectively. Wnt\/\u03b2\u2010catenin and TGF\u2010\u03b2\/SMAD pathways, both overactive in UL, promote stem cell self\u2010renewal, crosstalk between stem and mature cells, cellular proliferation, extracellular matrix (ECM) accumulation and drive overall UL growth. Recent evidence suggests that simvastatin, an antihyperlipidemic drug, may have anti\u2010leiomyoma properties. Herein, we investigated the effects of simvastatin on UL stem cells. We isolated leiomyoma stem cells by flow cytometry using DyeCycle Violet staining and Stro\u20101\/CD44\u00a0surface markers. We found that simvastatin inhibits proliferation and induces apoptosis in UL stem cells. In addition, it also suppressed the expression of the stemness markers Nanog, Oct4 and Sox2. Simvastatin significantly decreased the production of the key ECM proteins, collagen 1 and fibronectin. Finally, it inhibited genes and\/or proteins expression of TGF\u2010\u03b21, 2 and 3, SMAD2, SMAD4, Wnt4, \u03b2\u2010Catenin, LRP6, AXIN2 and Cyclin D1 in UL stem cells, all are key drivers of the TGF\u2010\u03b23\/SMAD2 and Wnt4\/\u03b2\u2010Catenin pathways. Thus, we have identified a novel stem cell\u2010targeting anti\u2010leiomyoma simvastatin effect. Further studies are needed to replicate these findings <jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/jcmm.17211","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T09:50:16Z","timestamp":1643968216000},"page":"1684-1698","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Simvastatin inhibits stem cell proliferation in human leiomyoma via TGF\u2010\u03b23 and Wnt\/\u03b2\u2010Catenin pathways"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5063-9900","authenticated-orcid":false,"given":"Sadia","family":"Afrin","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Ali","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department Faculty of Pharmacy Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malak","family":"El Sabeh","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiwei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics University of Chicago School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"Al\u2010Hendy","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics University of Chicago School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-132X","authenticated-orcid":false,"given":"Mostafa A.","family":"Borahay","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland 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