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In this study, we tested the role of retinoic acid-related orphan receptor \u03b3 (ROR\u03b3), which is expressed in skin, in the action of CYP11A1-derived secosteroids using murine fibroblasts isolated from the skin of wild-type (ROR\u03b3\u200a+\/+), knockout (ROR\u03b3\u200a-\/-), and heterozygote (ROR\u03b3\u200a+\/-) mice. CYP11A1-derived 20(OH)D3, 20,23(OH)2D3, 1,20(OH)2D3, and 1,20,23(OH)3D3 inhibited proliferation of ROR\u03b3\u200a+\/+ fibroblasts in a dose-dependent manner with a similar potency to 1,25(OH)2D3. Surprisingly, this effect was reversed in ROR\u03b3\u200a+\/- and ROR\u03b3\u200a-\/- fibroblasts, with the most pronounced stimulatory effect seen in ROR\u03b3\u200a-\/- fibroblasts. All analogs tested inhibited TGF-\u03b21-induced collagen synthesis in ROR\u03b3\u200a+\/+ fibroblasts and the expression of other fibrosis-related genes. This effect was curtailed or reversed in ROR\u03b3\u200a-\/- fibroblasts. These results show that the antiproliferative and antifibrotic activities of the vitamin D hydroxy derivatives are dependent on a functional ROR\u03b3. The dramatic changes in the transcriptomes of fibroblasts of ROR\u03b3\u200a-\/- versus wild-type mice following treatment with 20(OH)D3 or 1,20(OH)2D3 provide a molecular basis to explain, at least in part, the observed phenotypic differences.<\/jats:p>","DOI":"10.1210\/endocr\/bqaa198","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T10:10:53Z","timestamp":1603793453000},"source":"Crossref","is-referenced-by-count":27,"title":["Antifibrogenic Activities of CYP11A1-derived Vitamin D3-hydroxyderivatives Are Dependent on ROR\u03b3"],"prefix":"10.1210","volume":"162","author":[{"given":"Zorica","family":"Janjetovic","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold","family":"Postlethwaite","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Science 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