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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2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8926 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Monica L. Brown Lobbins |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T08:43:50Z |
| format | Article |
| id | doaj.art-586caac290d64398abc0326b37197255 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:43:50Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-586caac290d64398abc0326b371972552023-11-22T08:02:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216892610.3390/ijms2216892617,20S(OH)<sub>2</sub>pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse ModelMonica L. Brown Lobbins0Imara-Safi O. Scott1Andrzej T. Slominski2Karen A. Hasty3Sicheng Zhang4Duane D. Miller5Wei Li6Tae-Kang Kim7Zorica Janjetovic8Tejesh S. Patel9Linda K. Myers10Arnold E. Postlethwaite11Departments of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartments of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartments of Dermatology, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USADepartments of Orthopedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USADepartment of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USADepartment of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USADepartments of Dermatology, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USADepartments of Dermatology, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USADepartment of Dermatology, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartments of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartments of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USASystemic 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.https://www.mdpi.com/1422-0067/22/16/8926vitamin DsclerodermaTGF-β1bleomycin model of fibrosiscollagencytokines |
| spellingShingle | 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 17,20S(OH)<sub>2</sub>pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse Model International Journal of Molecular Sciences vitamin D scleroderma TGF-β1 bleomycin model of fibrosis collagen cytokines |
| title | 17,20S(OH)<sub>2</sub>pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse Model |
| title_full | 17,20S(OH)<sub>2</sub>pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse Model |
| title_fullStr | 17,20S(OH)<sub>2</sub>pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse Model |
| title_full_unstemmed | 17,20S(OH)<sub>2</sub>pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse Model |
| title_short | 17,20S(OH)<sub>2</sub>pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse Model |
| title_sort | 17 20s oh sub 2 sub pd can prevent the development of skin fibrosis in the bleomycin induced scleroderma mouse model |
| topic | vitamin D scleroderma TGF-β1 bleomycin model of fibrosis collagen cytokines |
| url | https://www.mdpi.com/1422-0067/22/16/8926 |
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