Published August 18, 2020 | Version v1
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Supplemental tables from: Antifibrogenic activities of CYP11A1-derived vitamin D3-hydroxyderivatives are dependent on RORγ

  • 1. University of Alabama at Birmingham
  • 2. University of Tennessee Health Science Center
  • 3. National Institutes of Health
  • 4. University of Western Australia


Previous studies showed that non-calcemic 20(OH)D3, a product of CYP11A1 action on vitamin D3, has antifibrotic activity in human dermal fibroblasts and in a bleomycin mouse model of scleroderma. In this study we tested the role of RORγ, which is expressed in skin, in the action of CYP11A1-derived secosteroids using murine fibroblasts isolated from the skin of wild type (RORg+/+), knock out (RORg-/-) and heterozygote (RORg+/-) mice. CYP11A1-derived 20(OH)D3, 20,23(OH)2D3, 1,20(OH)2D3, and 1,20,23(OH)3D3 inhibited proliferation of RORγ+/+ fibroblasts in a dose-dependent manner with a similar potency to 1,25(OH)2D3. Surprisingly, this effect was reversed in RORγ+/- and RORγ-/- fibroblasts with the most pronounced stimulatory effect seen in RORγ-/- fibroblasts. All of the analogs tested inhibited TGF-β1-induced collagen synthesis in RORγ+/+ fibroblasts and the expression of other fibrosis-related genes. This effect was curtailed or reversed in RORγ-/- fibroblasts. These results show that the antiproliferative and antifibrotic activities of the vitamin D hydroxy-derivatives are dependent on a functional RORγ. The dramatic changes in the transcriptomes of fibroblasts of RORg-/- versus wild type mice following treatment with 20(OH)D3 or 1,20(OH)2D3 provide a molecular basis to explain, at least in part, the observed phenotypic differences


Funding provided by: National Institutes of Health
Crossref Funder Registry ID:
Award Number: 1RO1 AR052190 and 1R21 AR0665051

Funding provided by: U.S. Department of Veterans Affairs
Crossref Funder Registry ID:
Award Number: 1I01BX004293-01A1

Funding provided by: National Institutes of Health
Crossref Funder Registry ID:
Award Number: 1R01AR073004-01A1 and R01AR071189-01A1


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