Modulation by 17,20S(OH)<sub>2</sub>pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic Sclerosis
We previously demonstrated that the non-calcemic pregnacalciferol (pD) analog 17,20S (OH)<sub>2</sub>pD suppressed TGF-β1-induced type I collagen production in cultured normal human dermal fibroblasts. In the present studies, we examined fibroblasts cultured from the lesional skin of pat...
| Main Authors: | , , , , , , , , , , , |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/1/367 |
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| author | Monica L. Brown Lobbins Andrzej T. Slominski Karen A. Hasty Sicheng Zhang Duane D. Miller Wei Li Tae-Kang Kim Zorica Janjetovic Robert C. Tuckey Imara-Safi O. Scott Linda K. Myers Arnold E. Postlethwaite |
| author_facet | Monica L. Brown Lobbins Andrzej T. Slominski Karen A. Hasty Sicheng Zhang Duane D. Miller Wei Li Tae-Kang Kim Zorica Janjetovic Robert C. Tuckey Imara-Safi O. Scott Linda K. Myers Arnold E. Postlethwaite |
| author_sort | Monica L. Brown Lobbins |
| collection | DOAJ |
| description | We previously demonstrated that the non-calcemic pregnacalciferol (pD) analog 17,20S (OH)<sub>2</sub>pD suppressed TGF-β1-induced type I collagen production in cultured normal human dermal fibroblasts. In the present studies, we examined fibroblasts cultured from the lesional skin of patients with systemic sclerosis (scleroderma (SSc)) and assessed the effects of 17,20S(OH)<sub>2</sub>pD on fibrosis-related mediators. Dermal fibroblast lines were established from skin biopsies from patients with SSc and healthy controls. Fibroblasts were cultured with either 17,20S(OH)<sub>2</sub>pD or 1,25(OH)<sub>2</sub>D<sub>3</sub> (positive control) with/without TGF-β1 stimulation and extracted for protein and/or mRNA for collagen synthesis and mediators of fibrosis (MMP-1, TIMP-1, PAI-1, BMP-7, PGES, GLI1, and GLI2). 1 7,20S(OH)<sub>2</sub>pD (similar to 1,25(OH)<sub>2</sub>D<sub>3</sub>) significantly suppressed net total collagen production in TGF-β1-stimulated normal donor fibroblast cultures and in cultures of SSc dermal fibroblasts. 17,20S(OH)<sub>2</sub>pD (similar to 1,25(OH)<sub>2</sub>D<sub>3</sub>) also increased MMP-1, BMP-7, and PGES and decreased TIMP-1 and PAI1 expression in SSc fibroblasts. Although 17,20S(OH)<sub>2</sub>pD had no effect on Gli1 or Gli2 in SSc fibroblasts, it increased Gli2 expression when cultured with TGF-β1 in normal fibroblasts. These studies demonstrated that 17,20S(OH)<sub>2</sub>pD modulates mediators of fibrosis to favor the reduction of fibrosis and may offer new noncalcemic secosteroidal therapeutic approaches for treating SSc and fibrosis. |
| first_indexed | 2024-03-10T03:39:01Z |
| format | Article |
| id | doaj.art-c7bce4db2efe4d68b05ba81c56c86282 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:39:01Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c7bce4db2efe4d68b05ba81c56c862822023-11-23T11:38:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0123136710.3390/ijms23010367Modulation by 17,20S(OH)<sub>2</sub>pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic SclerosisMonica L. Brown Lobbins0Andrzej T. Slominski1Karen A. Hasty2Sicheng Zhang3Duane D. Miller4Wei Li5Tae-Kang Kim6Zorica Janjetovic7Robert C. Tuckey8Imara-Safi O. Scott9Linda K. Myers10Arnold E. Postlethwaite11Department of Pediatrics, University of Tennessee Health Science Center, 50 N. Dunlap, Rm. 461R, Memphis, TN 38103, USADepartment of Dermatology, University of Alabama at Birmingham, 500 22nd Street South, Birmingham, AL 35294, USAMemphis Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104, USADepartment of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38103, USADepartment of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38103, USADepartment of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38103, USADepartment of Dermatology, University of Alabama at Birmingham, 500 22nd Street South, Birmingham, AL 35294, USADepartment of Dermatology, University of Alabama at Birmingham, 500 22nd Street South, Birmingham, AL 35294, USASchool of Molecular Sciences, University of Western Australia, 35 Stirling Highway, Perth 6009, AustraliaDepartment of Medicine, University of Tennessee Health Science Center, 956 Court Avenue, Memphis, TN 38163, USADepartment of Pediatrics, University of Tennessee Health Science Center, 50 N. Dunlap, Rm. 461R, Memphis, TN 38103, USADepartment of Medicine, University of Tennessee Health Science Center, 956 Court Avenue, Memphis, TN 38163, USAWe previously demonstrated that the non-calcemic pregnacalciferol (pD) analog 17,20S (OH)<sub>2</sub>pD suppressed TGF-β1-induced type I collagen production in cultured normal human dermal fibroblasts. In the present studies, we examined fibroblasts cultured from the lesional skin of patients with systemic sclerosis (scleroderma (SSc)) and assessed the effects of 17,20S(OH)<sub>2</sub>pD on fibrosis-related mediators. Dermal fibroblast lines were established from skin biopsies from patients with SSc and healthy controls. Fibroblasts were cultured with either 17,20S(OH)<sub>2</sub>pD or 1,25(OH)<sub>2</sub>D<sub>3</sub> (positive control) with/without TGF-β1 stimulation and extracted for protein and/or mRNA for collagen synthesis and mediators of fibrosis (MMP-1, TIMP-1, PAI-1, BMP-7, PGES, GLI1, and GLI2). 1 7,20S(OH)<sub>2</sub>pD (similar to 1,25(OH)<sub>2</sub>D<sub>3</sub>) significantly suppressed net total collagen production in TGF-β1-stimulated normal donor fibroblast cultures and in cultures of SSc dermal fibroblasts. 17,20S(OH)<sub>2</sub>pD (similar to 1,25(OH)<sub>2</sub>D<sub>3</sub>) also increased MMP-1, BMP-7, and PGES and decreased TIMP-1 and PAI1 expression in SSc fibroblasts. Although 17,20S(OH)<sub>2</sub>pD had no effect on Gli1 or Gli2 in SSc fibroblasts, it increased Gli2 expression when cultured with TGF-β1 in normal fibroblasts. These studies demonstrated that 17,20S(OH)<sub>2</sub>pD modulates mediators of fibrosis to favor the reduction of fibrosis and may offer new noncalcemic secosteroidal therapeutic approaches for treating SSc and fibrosis.https://www.mdpi.com/1422-0067/23/1/367vitamin DsclerodermaTGF-β1fibrosiscollagen |
| spellingShingle | Monica L. Brown Lobbins Andrzej T. Slominski Karen A. Hasty Sicheng Zhang Duane D. Miller Wei Li Tae-Kang Kim Zorica Janjetovic Robert C. Tuckey Imara-Safi O. Scott Linda K. Myers Arnold E. Postlethwaite Modulation by 17,20S(OH)<sub>2</sub>pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic Sclerosis International Journal of Molecular Sciences vitamin D scleroderma TGF-β1 fibrosis collagen |
| title | Modulation by 17,20S(OH)<sub>2</sub>pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic Sclerosis |
| title_full | Modulation by 17,20S(OH)<sub>2</sub>pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic Sclerosis |
| title_fullStr | Modulation by 17,20S(OH)<sub>2</sub>pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic Sclerosis |
| title_full_unstemmed | Modulation by 17,20S(OH)<sub>2</sub>pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic Sclerosis |
| title_short | Modulation by 17,20S(OH)<sub>2</sub>pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic Sclerosis |
| title_sort | modulation by 17 20s oh sub 2 sub pd of fibrosis related mediators in dermal fibroblast lines from healthy donors and from patients with systemic sclerosis |
| topic | vitamin D scleroderma TGF-β1 fibrosis collagen |
| url | https://www.mdpi.com/1422-0067/23/1/367 |
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