{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:23:32Z","timestamp":1792646612039,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Stem Cells International"],"published-print":{"date-parts":[[2021,6,22]]},"abstract":"<jats:p>Oral submucous fibrosis (OSF) is a precancerous lesion. Adipose-derived stem cell- (ADSC-) derived extracellular vesicles (EVs) (ADSC-EVs) regulate multiple oral diseases. Hence, this study explored the mechanism of ADSC-EVs in OSF. ADSCs were transduced with microRNA- (miR-) 375 mimic. ADSC-EVs and miR-375-overexpressed ADSC-EVs (EVs-miR-375) were extracted and identified. miR-375 expression in EVs and fibrotic buccal mucosal fibroblasts (fBMFs) was detected. EV uptake by fBMFs was observed. The targeted relationship between miR-375 and forkhead box protein F1 (FOXF1) was predicted and verified. After EVs-miR-375 treatment or FOXF1 overexpression, fBMF cell proliferation, migration, invasion, and apoptosis were evaluated, and levels of apoptosis-related proteins (cleaved-caspase-3, Bax, and Bcl-2) and fibrosis markers (\u03b1-SMA, collagen I, and collagen III) were detected. Functional rescue experiments were further performed to verify the role of the miR-375\/FOXF1 axis in OSF. miR-375 was notably upregulated in EVs-miR-375 and EVs-miR-375-treated fBMFs (all <jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>P<\/a:mi>\n                        <a:mo>&lt;<\/a:mo>\n                        <a:mn>0.001<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula>). ADSC-EVs carried miR-375 into fBMFs. fBMFs can internalize ADSC-EVs. EVs-miR-375 treatment markedly inhibited fBMF cell proliferation, migration, invasion, and fibrosis and promoted apoptosis (all <jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mi>P<\/c:mi>\n                        <c:mo>&lt;<\/c:mo>\n                        <c:mn>0.01<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula>). Moreover, miR-375 targeted FOXF1 in fBMFs. FOXF1 overexpression promoted fBMF cell biological behaviors and fibrosis, which were reversed after EVs-miR-375 treatment (<jats:inline-formula>\n                     <e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                        <e:mi>P<\/e:mi>\n                        <e:mo>&lt;<\/e:mo>\n                        <e:mn>0.01<\/e:mn>\n                     <\/e:math>\n                  <\/jats:inline-formula> or <jats:inline-formula>\n                     <g:math xmlns:g=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\">\n                        <g:mi>P<\/g:mi>\n                        <g:mo>&lt;<\/g:mo>\n                        <g:mn>0.001<\/g:mn>\n                     <\/g:math>\n                  <\/jats:inline-formula>). We highlighted that ADSC-EVs inhibited fBMF fibrosis and then suppressed OSF progression via the miR-375\/FOXF1 axis.<\/jats:p>","DOI":"10.1155\/2021\/9964159","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T18:35:14Z","timestamp":1624473314000},"page":"1-15","source":"Crossref","is-referenced-by-count":16,"title":["Adipose-Derived Stem Cell-Derived Extracellular Vesicles Inhibit the Fibrosis of Fibrotic Buccal Mucosal Fibroblasts via the MicroRNA-375\/FOXF1 Axis"],"prefix":"10.1155","volume":"2021","author":[{"given":"Bin","family":"Han","sequence":"first","affiliation":[{"name":"Department of Stomatology, Rizhao People\u2019s Hospital, Rizhao, 276826 Shandong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Rizhao People\u2019s Hospital, Rizhao, 276826 Shandong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3025-1532","authenticated-orcid":true,"given":"Yuxia","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Rizhao People\u2019s Hospital, Rizhao, 276826 Shandong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Rizhao People\u2019s Hospital, Rizhao, 276826 Shandong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Rizhao People\u2019s Hospital, Rizhao, 276826 Shandong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Rizhao People\u2019s Hospital, Rizhao, 276826 Shandong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.4103\/jcrt.JCRT_522_17"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12924"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12581"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.4103\/0973-1482.179524"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12266"},{"key":"6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2147\/CCID.S80576","article-title":"Oral submucous fibrosis: an update","volume":"8","author":"U. 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