{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T19:51:02Z","timestamp":1774986662634,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIAMS NIH","award":["AR066505, AR071189, AR073004,"],"award-info":[{"award-number":["AR066505, AR071189, AR073004,"]}]},{"name":"National Scleroderma Foundation","award":["program directed funds"],"award-info":[{"award-number":["program directed funds"]}]},{"DOI":"10.13039\/100000980","name":"Arthritis Foundation","doi-asserted-by":"publisher","award":["program directed funds"],"award-info":[{"award-number":["program directed funds"]}],"id":[{"id":"10.13039\/100000980","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["S1P1BX001607"],"award-info":[{"award-number":["S1P1BX001607"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic sclerosis (SSc; scleroderma) is a chronic fibrotic disease involving TGF-\u03b21. Low serum vitamin D (vit D) correlates with the degree of fibrosis and expression of TGF-\u03b21. This study was designed to determine whether the noncalcemic vit D analog, 17,20S(OH)2pD, suppresses fibrosis and mediators of the TGF-\u03b21 pathway in the bleomycin (BLM) model of fibrosis. Fibrosis was induced into the skin of female C57BL\/6 mice by repeated injections of BLM (50 \u03bcg\/100 \u03bcL) subcutaneously. Mice received daily oral gavage with either vehicle (propylene glycol) or 17,20S(OH)2pD using 5, 15, or 30 \u03bcg\/kg for 21 days. The injected skin was biopsied; analyzed histologically; examined for total collagen by Sircol; and examined for mRNA expression of MMP-13, BMP-7, MCP-1, Gli1, and Gli2 by TR-PCR. Spleen was analyzed for lymphocytes using flow cytometry. Serum was analyzed for cytokines using a multiplexed ELISA. Results showed that all three doses of 17,20S(OH)2pD suppressed net total collagen production, dermal thickness, and total collagen content in the BLM fibrosis model. 17,20S(OH)2pD also increased MMP-13 expression, decreased MCP-1 and Gli-2 expression in vivo, and suppressed serum levels of IL-13, TNF-\u03b1, IL-6, IL-10, IL-17, and IL-12p70. In summary, 17,20S(OH)2pD modulates the mediators of fibrosis in vivo and suppresses total collagen production and dermal thickness. This antifibrotic property of 17,20S(OH)2pD offers new therapeutic approaches for fibrotic disorders.<\/jats:p>","DOI":"10.3390\/ijms22168926","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T09:58:06Z","timestamp":1629367086000},"page":"8926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["17,20S(OH)2pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse Model"],"prefix":"10.3390","volume":"22","author":[{"given":"Monica L.","family":"Brown Lobbins","sequence":"first","affiliation":[{"name":"Departments of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA"},{"name":"Departments of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imara-Safi O.","family":"Scott","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8963-3995","authenticated-orcid":false,"given":"Andrzej T.","family":"Slominski","sequence":"additional","affiliation":[{"name":"Departments of Dermatology, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USA"},{"name":"O\u2019Neal Comprehensive Cancer Center, University of Alabama at Birmingham, 1824 6th Ave., Birmingham, AL 35294, USA"},{"name":"Birmingham VA Medical Center, 700 19th Street S., Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen A.","family":"Hasty","sequence":"additional","affiliation":[{"name":"Departments of Orthopedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN 38163, USA"},{"name":"VA Medical Center, 1030 Jefferson Ave, Memphis, TN 38104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3798-7550","authenticated-orcid":false,"given":"Sicheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6093-0985","authenticated-orcid":false,"given":"Duane D.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9522-4474","authenticated-orcid":false,"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1394-4134","authenticated-orcid":false,"given":"Tae-Kang","family":"Kim","sequence":"additional","affiliation":[{"name":"Departments of Dermatology, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6108-2212","authenticated-orcid":false,"given":"Zorica","family":"Janjetovic","sequence":"additional","affiliation":[{"name":"Departments of Dermatology, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tejesh S.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda K.","family":"Myers","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA"},{"name":"Departments of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold E.","family":"Postlethwaite","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"},{"name":"VA Medical Center, 1030 Jefferson Ave, Memphis, TN 38104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"272","DOI":"10.3389\/fimmu.2015.00272","article-title":"Pathogenesis of systemic sclerosis","volume":"6","author":"Pattanaik","year":"2015","journal-title":"Front. 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