{"doi":"10.1210/endocr/bqaa198","title":"Antifibrogenic Activities of CYP11A1-derived Vitamin D3-hydroxyderivatives Are Dependent on RORγ","abstract":"Previous studies showed that noncalcemic 20(OH)D3, a product of CYP11A1 action on vitamin D3, has antifibrotic activity in human dermal fibroblasts and in a bleomycin mouse model of scleroderma. In this study, we tested the role of retinoic acid-related orphan receptor γ (RORγ), which is expressed in skin, in the action of CYP11A1-derived secosteroids using murine fibroblasts isolated from the skin of wild-type (RORγ +/+), knockout (RORγ -/-), and heterozygote (RORγ +/-) mice. CYP11A1-derived 20(OH)D3, 20,23(OH)2D3, 1,20(OH)2D3, and 1,20,23(OH)3D3 inhibited proliferation of RORγ +/+ fibroblasts in a dose-dependent manner with a similar potency to 1,25(OH)2D3. Surprisingly, this effect was reversed in RORγ +/- and RORγ -/- fibroblasts, with the most pronounced stimulatory effect seen in RORγ -/- fibroblasts. All analogs tested inhibited TGF-β1-induced collagen synthesis in RORγ +/+ fibroblasts and the expression of other fibrosis-related genes. This effect was curtailed or reversed in RORγ -/- fibroblasts. These results show that the antiproliferative and antifibrotic activities of the vitamin D hydroxy derivatives are dependent on a functional RORγ. The dramatic changes in the transcriptomes of fibroblasts of RORγ -/- 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.","journal":"Endocrinology","year":2020,"id":102691,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":257556,"name":"Arnold E. Postlethwaite","orcid":"0000-0002-5952-0161","position":1,"is_corresponding":false},{"id":349041,"name":"Hong Soon Kang","orcid":"0000-0003-2230-8797","position":2,"is_corresponding":false},{"id":259109,"name":"Tae‐Kang Kim","orcid":"0000-0003-1394-4134","position":3,"is_corresponding":false},{"id":257554,"name":"Robert C. Tuckey","orcid":"0000-0002-5022-4729","position":4,"is_corresponding":false},{"id":254085,"name":"David K. Crossman","orcid":"0000-0002-0981-169X","position":5,"is_corresponding":false},{"id":259112,"name":"Shariq Qayyum","orcid":"0000-0003-0777-1994","position":6,"is_corresponding":false},{"id":97236,"name":"Anton M. Jetten","orcid":"0000-0003-0954-4445","position":7,"is_corresponding":false},{"id":97237,"name":"Andrzej Słomiński","orcid":"0000-0001-8963-3995","position":8,"is_corresponding":false},{"id":259108,"name":"Zorica Janjetović","orcid":"0000-0001-6108-2212","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T22:41:53.173268Z","pmid":"33107570","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}