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

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

PROVIDER: PRJNA918728 | ENA |

REPOSITORIES: ENA

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

Project description:Antifibrogenic activities of CYP11A1-derived vitamin D3-hydroxyderivatives are modified by RORγ expression

| PRJNA918726 | ENA

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

Project description:Antifibrogenic activities of CYP11A1-derived vitamin D3-hydroxyderivatives are modified by RORγ expression [I]

| PRJNA608446 | ENA

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

Project description: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.

2024-01-07 | GSE222269 | GEO

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

2020-12-31 | GSE145818 | GEO

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-01-06 | GSE222270 | GEO

Antifibrogenic Activities of CYP11A1-derived Vitamin D3-hydroxyderivatives Are Dependent on RORγ.

Project description:Previous studies showed that noncalcemic 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 retinoic acid-related orphan receptor γ (RORγ), which is expressed in skin, in the action of CYP11A1-derived secosteroids using murine fibroblasts isolated from the skin of wild-type (RORγ +/+), knockout (RORγ -/-), and heterozygote (RORγ +/-) 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 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 RORγ -/- 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.

| S-EPMC7717072 | biostudies-literature

Natural compounds ursolic acid and digoxin exhibit inhibitory activities to cancer cells in RORγ-dependent and -independent manner

Project description:Natural compounds ursolic acid (UA) and digoxin isolated from fruits and other plants display potent anti-cancer effects in preclinical studies. UA and digoxin have been at clinical trials for treatment of different cancers including prostate cancer, pancreatic cancer and breast cancer. However, they displayed limited benefit to patients. Currently, a poor understanding of their direct targets and mechanisms of action (MOA) severely hinders their further development. We previously identified nuclear receptor RORγ as a novel therapeutic target for castration-resistant prostate cancer (CRPC) and triple-negative breast cancer (TNBC) and demonstrated that tumor cell RORγ directly activates gene programs such as androgen receptor (AR) signaling and cholesterol metabolism. Previous studies also demonstrated that UA and digoxin are potential RORγt antagonists in modulating the functions of immune cells such as Th17 cells. Here we showed that UA displays a strong activity in inhibition of RORγ-dependent transactivation function in cancer cells, while digoxin exhibits no effect at clinically relevant concentrations. In prostate cancer cells, UA down-regulates RORγ-stimulated AR expression and AR signaling, whereas digoxin up-regulates AR signaling pathway. In TNBC cells, UA but not digoxin alters RORγ-controlled gene programs of cell proliferation, apoptosis and cholesterol-biosynthesis.Together, our study reveals for the first-time that UA, but not digoxin, acts as a natural antagonist of RORγ in the cancer cells. Our finding that RORγ is a direct target of UA in cancer cells will help select patients with tumors that likely respond to UA treatment.

2023-05-17 | GSE230039 | GEO

Transcriptome profiling of gingival fibroblasts treated by vitamin D3

Project description:In humans, vitamin D3 is a secosteroid, a prohormonal precursor of biologically active hydroxyforms. Vitamin D3 is related to periodontitis. The third American Health and Nutrition Survey found that plasma 25(OH)D3 levels are negatively correlated with attachment loss in people aged >50 years. The relationship between vitamin D3 and periodontitis remains to be investigated. We sent human gingival fibroblasts treated by vitamin D3 for transcriptome sequencing.

2022-09-09 | GSE212728 | GEO

scRNAseq of Cyp11a1-expressing cells from mouse melanoma model derived tumors

Project description:Tumours induce de novo steroidogenesis in immune cells. We wanted to define the gene expression identity of intratumoural steroidogenic immune cells and compare them with the transcriptome with non-steroidogenic cells. Cyp11a1 expression is a faithful biomarker of de novo steroidogenesis (i.e. Cyp11a1+ cells are steroidogenic and Cyp11a1- cells are non-steroidogenic). We inoculated B16-F10 tumor in Cyp11a1-mCherry reporter mice, enriched and purified intratumoral Cyp11a1-mCherry+ and Cyp11a1-mCherry- cells by cell sorting into 96-well plates [with a ratio of 79:15 (mCherry+ : mCherry-) cells per plate] and performed scRNA-seq using SMART-Seq2 platform.

2020-05-27 | E-MTAB-8509 | biostudies-arrayexpress

e18.5 pancreas: WT vs Cyp11a1 KO

Project description:RNA profiling of WT and cyp11a1 KO pancreas at e18.5

2021-06-25 | GSE178633 | GEO