17,20S(OH)<sub>2</sub>pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse Model

17,20S(OH)<sub>2</sub>pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse Model

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)<sub>2</sub>pD, suppress...

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Bibliographic Details
Main Authors: Monica L. Brown Lobbins, Imara-Safi O. Scott, Andrzej T. Slominski, Karen A. Hasty, Sicheng Zhang, Duane D. Miller, Wei Li, Tae-Kang Kim, Zorica Janjetovic, Tejesh S. Patel, Linda K. Myers, Arnold E. Postlethwaite
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:International Journal of Molecular Sciences
Subjects:
vitamin D
scleroderma
TGF-β1
bleomycin model of fibrosis
collagen
cytokines
Online Access:https://www.mdpi.com/1422-0067/22/16/8926
Description
Summary: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)<sub>2</sub>pD, 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)<sub>2</sub>pD 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)<sub>2</sub>pD suppressed net total collagen production, dermal thickness, and total collagen content in the BLM fibrosis model. 17,20S(OH)<sub>2</sub>pD 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)<sub>2</sub>pD modulates the mediators of fibrosis in vivo and suppresses total collagen production and dermal thickness. This antifibrotic property of 17,20S(OH)<sub>2</sub>pD offers new therapeutic approaches for fibrotic disorders.
ISSN:1661-6596
1422-0067

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