{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T19:51:01Z","timestamp":1774986661152,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T00:00:00Z","timestamp":1640736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R21AR066505, R01AR071189, R01AR073004, R21 AI149267"],"award-info":[{"award-number":["R21AR066505, R01AR071189, R01AR073004, R21 AI149267"]}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["5IP1BX001607-01 , BX004293, BX004151"],"award-info":[{"award-number":["5IP1BX001607-01 , BX004293, BX004151"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001844","name":"Scleroderma Foundation","doi-asserted-by":"publisher","award":["R073223552"],"award-info":[{"award-number":["R073223552"]}],"id":[{"id":"10.13039\/100001844","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Tennessee College of Pharmacy Drug Discovery Center","award":["general fundds"],"award-info":[{"award-number":["general fundds"]}]},{"name":"Arthritis Foundatioin","award":["Biomedical Research Grant"],"award-info":[{"award-number":["Biomedical Research Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We previously demonstrated that the non-calcemic pregnacalciferol (pD) analog 17,20S (OH)2pD suppressed TGF-\u03b21-induced type I collagen production in cultured normal human dermal fibroblasts. In the present studies, we examined fibroblasts cultured from the lesional skin of patients with systemic sclerosis (scleroderma (SSc)) and assessed the effects of 17,20S(OH)2pD on fibrosis-related mediators. Dermal fibroblast lines were established from skin biopsies from patients with SSc and healthy controls. Fibroblasts were cultured with either 17,20S(OH)2pD or 1,25(OH)2D3 (positive control) with\/without TGF-\u03b21 stimulation and extracted for protein and\/or mRNA for collagen synthesis and mediators of fibrosis (MMP-1, TIMP-1, PAI-1, BMP-7, PGES, GLI1, and GLI2). 1 7,20S(OH)2pD (similar to 1,25(OH)2D3) significantly suppressed net total collagen production in TGF-\u03b21-stimulated normal donor fibroblast cultures and in cultures of SSc dermal fibroblasts. 17,20S(OH)2pD (similar to 1,25(OH)2D3) also increased MMP-1, BMP-7, and PGES and decreased TIMP-1 and PAI1 expression in SSc fibroblasts. Although 17,20S(OH)2pD had no effect on Gli1 or Gli2 in SSc fibroblasts, it increased Gli2 expression when cultured with TGF-\u03b21 in normal fibroblasts. These studies demonstrated that 17,20S(OH)2pD modulates mediators of fibrosis to favor the reduction of fibrosis and may offer new noncalcemic secosteroidal therapeutic approaches for treating SSc and fibrosis.<\/jats:p>","DOI":"10.3390\/ijms23010367","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T23:31:35Z","timestamp":1640820695000},"page":"367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Modulation by 17,20S(OH)2pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic Sclerosis"],"prefix":"10.3390","volume":"23","author":[{"given":"Monica L.","family":"Brown Lobbins","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Tennessee Health Science Center, 50 N. Dunlap, Rm. 461R, Memphis, TN 38103, USA"},{"name":"Department of Medicine, University of Tennessee Health Science Center, 956 Court Avenue, 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":"Department of Dermatology, University of Alabama at Birmingham, 500 22nd Street South, Birmingham, AL 35294, USA"},{"name":"Comprehensive Cancer Center, University of Alabama at Birmingham, 1824 6th Avenue, Birmingham, AL 35294, USA"},{"name":"Birmingham Veterans Affairs Medical Center, 700 19th Street South, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen A.","family":"Hasty","sequence":"additional","affiliation":[{"name":"Memphis Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104, USA"},{"name":"Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, 1211 Union Avenue, Suite 520, 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 Avenue, Memphis, TN 38103, 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 Avenue, Memphis, TN 38103, 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 Avenue, Memphis, TN 38103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae-Kang","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Alabama at Birmingham, 500 22nd Street South, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zorica","family":"Janjetovic","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Alabama at Birmingham, 500 22nd Street South, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5022-4729","authenticated-orcid":false,"given":"Robert C.","family":"Tuckey","sequence":"additional","affiliation":[{"name":"School of Molecular Sciences, University of Western Australia, 35 Stirling Highway, Perth 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imara-Safi O.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Science Center, 956 Court Avenue, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5268-1870","authenticated-orcid":false,"given":"Linda K.","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Tennessee Health Science Center, 50 N. Dunlap, Rm. 461R, Memphis, TN 38103, USA"},{"name":"Department of Medicine, University of Tennessee Health Science Center, 956 Court Avenue, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold E.","family":"Postlethwaite","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Science Center, 956 Court Avenue, Memphis, TN 38163, USA"},{"name":"Memphis Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,29]]},"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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