Presenting Author Howard University, Howard University
Objective: This study investigates the protective properties of farsenoid X receptor (FXR) agonism by the drug Obeticholic Acid (OCA) in the adenine-induced tubulointerstitial fibrosis model of kidney disease male and female mice.
Hypothesis: OCA treatment will decrease the expression of SMAD3 and phosphorylated-SMAD3, and therefore will be nephroprotective in the adenine model of kidney disease in male and female mice.
Methods: Male and female C57BL/6J mice (12 weeks old) were fed chow (Research Diets D1912040li) or chow admixed with adenine (0.2% w/w) ad lib for 7 weeks. Mice were treated with either vehicle (corn oil) or obeticholic acid (10 mg/kg BW) by gavage 5 days per week. Plasma and organs were collected and processed for bio-chemical analysis.
Results: OCA treatment reduced BUN and plasma creatinine in diseased mice of both sexes. FXR agonism reduced SMAD3 expression in both male (Plt;0.05) and female (Plt;0.05) mice. Importantly, FXR agonism also reduced SMAD3 phosphorylation in both male (Plt;0.05) and female (Plt;0.001) mice. On histology, OCA reduced renal fibrosis in male (Plt;0.05) but not female mice.
Conclusions: FXR agonism by OCA is anti-fibrotic in the adenine model of tubulointerstitial fibrotic crystalline nephropathy in male and female mice. Mechanistically, OCA prevents renal fibrosis by reducing SMAD3 expression and phosphorylation.
