{"doi":"10.3390/ijms22168926","title":"17,20S(OH)2pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse Model","abstract":"Systemic sclerosis (SSc; scleroderma) is a chronic fibrotic disease involving TGF-β1. Low serum vitamin D (vit D) correlates with the degree of fibrosis and expression of TGF-β1. This study was designed to determine whether the noncalcemic vit D analog, 17,20S(OH)2pD, suppresses fibrosis and mediators of the TGF-β1 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 μg/100 μL) subcutaneously. Mice received daily oral gavage with either vehicle (propylene glycol) or 17,20S(OH)2pD using 5, 15, or 30 μg/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-α, 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.","journal":"International Journal of Molecular Sciences","year":2021,"id":188566,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9603,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":750448,"name":"Imara-Safi O. Scott","orcid":null,"position":1,"is_corresponding":false},{"id":97237,"name":"Andrzej Słomiński","orcid":"0000-0001-8963-3995","position":2,"is_corresponding":false},{"id":555416,"name":"Karen A. Hasty","orcid":"0000-0002-5049-6978","position":3,"is_corresponding":false},{"id":660530,"name":"Sicheng Zhang","orcid":"0000-0003-3798-7550","position":4,"is_corresponding":false},{"id":343727,"name":"Duane D. Miller","orcid":"0000-0002-6093-0985","position":5,"is_corresponding":false},{"id":242355,"name":"Wěi Li","orcid":"0000-0002-9522-4474","position":6,"is_corresponding":false},{"id":259109,"name":"Tae‐Kang Kim","orcid":"0000-0003-1394-4134","position":7,"is_corresponding":false},{"id":259108,"name":"Zorica Janjetović","orcid":"0000-0001-6108-2212","position":8,"is_corresponding":false},{"id":749752,"name":"Tejesh Patel","orcid":"0000-0001-7447-7379","position":9,"is_corresponding":false},{"id":460675,"name":"Linda K. Myers","orcid":"0000-0001-5268-1870","position":10,"is_corresponding":false},{"id":257556,"name":"Arnold E. Postlethwaite","orcid":"0000-0002-5952-0161","position":11,"is_corresponding":false},{"id":749751,"name":"Monica L. Brown Lobbins","orcid":"0000-0002-0362-9299","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T23:49:10.350554Z","pmid":"34445632","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":[]}