{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:02:26Z","timestamp":1792112546442,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To analyze the expression, regulation, and role of micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010125b (miR\u2010125b) in systemic sclerosis (<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MiR\u2010125b expression was assessed by quantitative polymerase chain reaction (<jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>) of <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> from dermal fibroblasts and whole skin biopsy specimens from healthy controls and <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c patients. To identify downstream effectors, <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> from healthy control fibroblasts was sequenced after miR\u2010125b knockdown and further validated using <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> and Western blotting. Fibrosis, apoptosis, and proliferation were assessed by Caspase\u2010Glo 3\/7 assay, Western blotting, immunofluorescence staining for cleaved caspase 3, and annexin V real\u2010time assay in dermal fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression of miR\u2010125b was significantly down\u2010regulated in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c skin biopsy specimens by 53% (median fold change 0.47 [interquartile range 0.35\u20130.69]; <jats:italic>P<\/jats:italic> &lt; 0.001) and in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c dermal fibroblasts by 47% (median fold change 0.53 [interquartile range 0.36\u20130.58]; <jats:italic>P<\/jats:italic> &lt; 0.001) compared to healthy control skin biopsy specimens and fibroblasts, respectively (n = 10 samples per group). Treatment with the histone deacetylase inhibitors trichostatin A and tubastatin A significantly decreased the expression of miR\u2010125b in dermal fibroblasts. MiR\u2010125b knockdown significantly reduced cell proliferation and \u03b1\u2010smooth muscle actin (\u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>) expression at the messenger <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>) and protein levels. <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010Seq identified <jats:italic><jats:styled-content style=\"fixed-case\">BAK<\/jats:styled-content>1<\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content><\/jats:italic>, and <jats:italic><jats:styled-content style=\"fixed-case\">BBC<\/jats:styled-content>3<\/jats:italic> as potential targets of miR\u2010125b. Quantitative <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> confirmed that knockdown of miR\u2010125b up\u2010regulated these genes (<jats:italic>P<\/jats:italic> &lt; 0.01; n = 12). Bcl\u20102 homologous antagonist killer 1 showed the strongest induction confirmed at the protein level (<jats:italic>P<\/jats:italic> &lt; 0.01; n = 10). Consequently, miR\u2010125b knockdown increased apoptosis compared to scrambled control. Accordingly, miR\u2010125b overexpression decreased apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that miR\u2010125b is down\u2010regulated in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c skin and primary dermal fibroblasts. MiR\u2010125b down\u2010regulation increases apoptosis and decreases proliferation and \u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> expression in dermal fibroblasts, indicating that its compensatory, antifibrotic mechanism may be a potential novel therapeutic option.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41041","type":"journal-article","created":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T03:45:47Z","timestamp":1563248747000},"page":"2068-2080","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Regulation of Fibroblast Apoptosis and Proliferation by Micro<scp>RNA<\/scp>\u2010125b in Systemic Sclerosis"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2413-1959","authenticated-orcid":false,"given":"Anastasiia","family":"Kozlova","sequence":"first","affiliation":[{"name":"University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5157-3808","authenticated-orcid":false,"given":"Elena","family":"Pachera","sequence":"additional","affiliation":[{"name":"University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9385-8097","authenticated-orcid":false,"given":"Britta","family":"Maurer","sequence":"additional","affiliation":[{"name":"University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"J\u00fcngel","sequence":"additional","affiliation":[{"name":"University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7408-9333","authenticated-orcid":false,"given":"J\u00f6rg H. 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