17,20S(OH)2pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse Model
Autor: | Andrzej Slominski, Imara-Safi O Scott, Duane D. Miller, Zorica Janjetovic, Wei Li, Arnold E. Postlethwaite, Linda K. Myers, Sicheng Zhang, Tejesh Patel, Monica L Brown Lobbins, Karen A. Hasty, Tae Kang Kim |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
collagen
medicine.medical_specialty QH301-705.5 Spleen vitamin D bleomycin model of fibrosis Bleomycin Skin Diseases Catalysis Oral gavage Scleroderma Article Flow cytometry Inorganic Chemistry chemistry.chemical_compound Mice In vivo Fibrosis Internal medicine TGF-β1 medicine Vitamin D and neurology Animals scleroderma Physical and Theoretical Chemistry Biology (General) skin and connective tissue diseases Molecular Biology QD1-999 Spectroscopy Cholecalciferol Antibiotics Antineoplastic Scleroderma Systemic medicine.diagnostic_test integumentary system Chemistry Organic Chemistry General Medicine medicine.disease cytokines Computer Science Applications Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Endocrinology Female |
Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 16 International Journal of Molecular Sciences, Vol 22, Iss 8926, p 8926 (2021) |
ISSN: | 1422-0067 |
DOI: | 10.3390/ijms22168926 |
Popis: | 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. |
Databáze: | OpenAIRE |
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