Transgenic overexpression of steroid sulfatase alleviates cholestasis

Abstract

Background and Aim Sulfotransferase (SULT)-mediated sulfation and steroid sulfatase (STS)-mediated desulfation represent two critical mechanisms that regulate the chemical and functional homeostasis of endogenous and exogenous molecules. STS catalyzes the hydrolysis of steroid sulfates to form hydroxysteroids. Oxygenated cholesterol derivative oxysterols are known to be endogenous ligands of the liver X receptor (LXR), a nuclear receptor with anti-cholestasis activity, whereas the sulfated oxysterols antagonize LXR signaling. The conversion of sulfated oxysterols to their non-sulfated counterparts is catalyzed by STS. The aim of this study is to determine whether STS can alleviate cholestasis by increasing the activity of LXR. Methods Liver-specific STS transgenic mice were created and subject to the lithocholic acid (LCA)-induced model of cholestasis. Results Transgenic overexpression of STS in the liver promoted bile acid elimination and alleviated LCA-induced cholestasis. The protective effect of the STS transgene was associated with the activation of LXR and induction of LXR target genes, likely because of the increased conversion of the antagonistic oxysterol sulfates to the agonistic oxysterols. Conclusions STS has a novel function in controlling the homeostasis of bile acids by regulating endogenous LXR ligands.

Identification of Metabolomic Biomarkers for Endometrial Cancer and Its Recurrence after Surgery in Postmenopausal Women

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Identification of metabolomic biomarkers for endometrial cancer and its recurrence after surgery in postmenopausal women

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MacrophageSult2b1promotes pathological neovascularization in age-related macular degeneration

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