Antifibrogenic activities of CYP11A1-derived vitamin D3-hydroxyderivatives are modified by RORγ expression [II]

The aim of this study was to test the role of RORγ in the action of the above analogs using murine fibroblasts isolated from the skin of wild type (RORg+/+) and knock out (RORg-/-) mice. mRNA profiles of fibroblasts isolated from the skin of the wild type (WT) and RORg-/- mice treated with CYP11A1- derived vitamin D3 derivatives: 20(OH)D3 and 1,20(OH)2D3 were generated by sequencing. We utilized RNA-sequencing in order to compare the gene expression profiles in wild type and RORγ-/- fibroblasts. Utilizing analysis we compared the gene expression profile of ethanol only treated RORγ-/- fibroblasts with ethanol treated RORγ+/+ fibroblasts. Analysis showed changes in five top canonical pathways including: role of BRCA1 in DNA damage response; Cell cycle: G2/M DNA damage checkpoint regulation; cell cycle control of chromosomal replication; mitotic roles of polo-like kinase; and hepatic fibrosis/ hepatic stellate cell activation. Among ingenuity’s biological functions and diseases and disorders, cancer, gastrointestinal diseases, organismal injury and abnormalities, reproductive system diseases, and hematological diseases are significantly affected. The main cellular functions that are affected are pertinent to liver and kidney inducing hepatotoxicity, renal toxicity, as well as cardiotoxicity.