{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:02:27Z","timestamp":1770832947879,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Key players mediating fibrosis are myofibroblasts (MF) that, following transforming growth factor \u03b2 (TGF\u03b2) exposure, produce a collagen-rich extracellular matrix (ECM) that induces myofibroblast differentiation. Myofibroblasts express \u03b1v\u03b23 integrin (a membrane receptor for thyroid hormones) and miRNA-21 that promotes deiodinase-type-3 expression (D3), causing the degradation of triiodothyronine (T3) that attenuates fibrosis. We hypothesized that \u03b1v\u03b23 affects the fibrotic processes through its thyroid hormones (THs) binding site. To test this, dermal fibroblasts (DF) were cultured with\/without TGF\u03b2 and removed with a base, leaving only normal\/fibrotic ECMs in wells. Then, DF were cultured on the ECMs with\/without tetrac (\u03b1v\u03b23 ligand, T4 antagonist), and evaluated for pro-fibrotic characteristics, \u03b1v\u03b23, miRNA-21, and D3 levels. Blood free-T3 (fT3), miRNA-21 levels, and the modified Rodnan skin score (MRSS) were evaluated in SSc patients. We found that the \u201cfibrotic-ECM\u201d significantly increased the pro-fibrotic characteristics of DF and the levels of miRNA-21, D3, and \u03b1v\u03b23, compared to the \u201cnormal-ECM.\u201d Tetrac significantly inhibited the effects of the \u201cfibrotic-ECM\u201d on the cells. In accordance with tetrac\u2019s effect on D3\/miRNA-21, a negative correlation was found between the patients\u2019 fT3 to miRNA-21 levels, and to the development of pulmonary arterial hypertension (PAH). We conclude that occupying the THs binding site of \u03b1v\u03b23 may delay the development of fibrosis.<\/jats:p>","DOI":"10.3390\/ijms24108927","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T08:09:44Z","timestamp":1684397384000},"page":"8927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["\u03b1v\u03b23 Integrin as a Link between the Development of Fibrosis and Thyroid Hormones in Systemic Sclerosis"],"prefix":"10.3390","volume":"24","author":[{"given":"Maia Yamila","family":"Kohon","sequence":"first","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Autoimmune Research Laboratory, Meir Medical Center, Kfar Saba 4428164, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mor","family":"Zaaroor Levy","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Autoimmune Research Laboratory, Meir Medical Center, Kfar Saba 4428164, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzipi","family":"Hornik-Lurie","sequence":"additional","affiliation":[{"name":"Data Research Department, Meir Medical Center, Kfar Saba 4428164, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avshalom","family":"Shalom","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Department of Plastic Surgery, Meir Medical Center, Kfar Saba 4428164, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3705-5454","authenticated-orcid":false,"given":"Ariel","family":"Berl","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Meir Medical Center, Kfar Saba 4428164, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liat","family":"Drucker","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Oncogenetics Laboratory, Meir Medical Center, Kfar Saba 4428164, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yair","family":"Levy","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Autoimmune Research Laboratory, Meir Medical Center, Kfar Saba 4428164, Israel"},{"name":"Department of Internal Medicine E, Meir Medical Center, Kfar Saba 4428164, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelly","family":"Tartakover Matalon","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Autoimmune Research Laboratory, Meir Medical Center, Kfar Saba 4428164, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/1346-8138.14153","article-title":"Systemic sclerosis","volume":"45","author":"Asano","year":"2018","journal-title":"J. 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