Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor

Abstract

Background: Patients with Crohn’s disease suffer from intestinal bile acid malabsorption. Intestinal bile acid absorption is mediated by the apical sodium dependent bile acid transporter ASBT/IBAT ( SLC10A2 ). In rats, ASBT is induced by glucocorticoids. Aims: To study whether human ASBT is activated by glucocorticoids and to elucidate the mechanism of regulation. Patients and methods: ASBT expression in ileal biopsies from patients with Crohn’s disease and from healthy subjects was quantified by western blot. ASBT promoter function was studied in luciferase assays and by electrophoretic mobility shift assay. Results: In 16 patients with Crohn’s disease, ASBT expression was reduced to 69 (7.5)% compared with healthy controls (mean (SEM); p = 0.01). In 10 healthy male volunteers, ASBT protein expression was increased 1.34 (0.11)-fold (mean (SEM); p Conclusions: Human ASBT is induced by glucocorticoids in vitro and in vivo. Induction of ASBT by glucocorticoids could be beneficial in patients with Crohn’s disease who exhibit reduced ASBT expression. This study identifies ASBT as a novel target of glucocorticoid controlled gene regulation in the human intestine.