{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:37:58Z","timestamp":1787585878794,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["111\u20102314\u2010B\u2010038\u2010092\u2010MY3"],"award-info":[{"award-number":["111\u20102314\u2010B\u2010038\u2010092\u2010MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Oral submucous fibrosis is characterized by excessive collagen deposition and is highly associated with a patient's betel nut chewing habit. Arecoline initiates the transforming growth factor\u2010beta (TGF\u2010\u03b2)\/Smads signaling pathway and activates downstream fibrotic genes. Dysregulation of microRNA (miR) expression is involved in the OSF progression, and miR modulation is a promising treatment. As one miR can target multiple mRNAs, and one mRNA has multiple binding sites to different miRs, we thus propose that simultaneous co\u2010transfection of anti\u2010fibrotic miRs may have a better therapeutic effect than single miR transfection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human oral fibroblasts were first subjected to arecoline stimulation and then transfected with 16 miRs individually. Based on the ability to downregulate <jats:italic>TGFB1<\/jats:italic> and actin alpha 2, smooth muscle (<jats:italic>ACTA2<\/jats:italic>) mRNA levels, the miR\u201029a\u20103p mimic, miR\u2010196a\u20103p mimic, and miR\u2010509\u20105p mimic were selected for co\u2010transfection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In addition to downregulation of collagen type I alpha 1 chain (<jats:italic>COL1A1<\/jats:italic>), <jats:italic>COL3A1<\/jats:italic>, <jats:italic>COL5A1<\/jats:italic>, matrix metalloproteinase\u20101 (<jats:italic>MMP1<\/jats:italic>), <jats:italic>MMP7<\/jats:italic>, tissue inhibitor of metalloproteinase\u20101 (<jats:italic>TIMP1<\/jats:italic>), and <jats:italic>TIMP2<\/jats:italic> mRNA expressions, co\u2010transfection with the three miRs led to a more significant downregulation of <jats:italic>COL1A1<\/jats:italic> and <jats:italic>MMP1<\/jats:italic> expressions. A Western blot analysis revealed that co\u2010transfection of the miRs efficiently suppressed the TGF\u2010\u03b2\/Smads pathway and extracellular matrix component productions. Furthermore, co\u2010transfection with miRs more effectively inhibited wound closure and collagen gel contraction compared to single miR transfection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Co\u2010transfection of anti\u2010fibrotic miRs can be a promising treatment for oral submucous fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.70009","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T03:16:27Z","timestamp":1750994187000},"page":"574-583","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Co\u2010Transfection With Anti\u2010Fibrotic <scp>microRNAs<\/scp> for Treating Oral Submucous Fibrosis"],"prefix":"10.1111","volume":"54","author":[{"given":"Chih\u2010Yuan","family":"Fang","sequence":"first","affiliation":[{"name":"School of Dentistry College of Oral Medicine, Taipei Medical University  Taipei Taiwan"},{"name":"Division of Oral and Maxillofacial Surgery, Department of Dentistry Wan Fang Hospital, Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin\u2010Ju","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science Chang Gung University  Taoyuan City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5143-2837","authenticated-orcid":false,"given":"Kuan\u2010Chou","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Dentistry College of Oral Medicine, Taipei Medical University  Taipei Taiwan"},{"name":"Division of Oral and Maxillofacial Surgery, Department of Dentistry Wan Fang Hospital, Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueh\u2010Hsin","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Dental Technology College of Oral Medicine, Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0979-4463","authenticated-orcid":false,"given":"Kai\u2010Chiang","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Dental Technology College of Oral Medicine, Taipei Medical University  Taipei Taiwan"},{"name":"Orthopedics Research Center Taipei Medical University Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27418"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6631856"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12663-014-0639-3"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijdr.IJDR_423_17"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20122940"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2019.12.010"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(01)00045-8"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e328354e559"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2020.10.019"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr182"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav1741"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2009.00881.x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/13880209.2016.1160251"},{"issue":"2","key":"e_1_2_11_15_1","first-page":"412","article-title":"Arecoline Induces ROS Accumulation, Transcription of Proinflammatory Factors, and Expression of KRT6 in Oral Epithelial Cells","volume":"12","author":"Wang T. 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