Induction of ABCA1 Expression by Liver X Receptor (LXR) agonist in Renal Glomerular Mesangial Cells

Abstract

Liver X receptors (LXRs) are hormone activated nuclear receptor transcription factors, which play an important role in regulating genes involved in fatty acid, cholesterol and glucose homeostasis. It has been recently reported that LXRs are expressed in the kidney. The present studies were designed to determine the expression and potential role of LXRs in cholesterol metabolism in mouse mesangial cells (MCs). MCs were cultured from mouse glomeruli. RT-PCR and immunoblot assays demonstrated that both LXR[alpha] and LXR[beta] are expressed in the MCs. A LXRE-luciferase reporter assay indicated that TO901317 treatment markedly increased LXRE activity, suggesting endogenous LXR receptors were functional in MCs. To further elucidate the role of LXRs in MCs, genome-wide gene expression profile was studied using the Affymetrix gene chip. The results demonstrated that there were 43 transcripts significantly regulated in the MCs by treatment of TO901317, a specific LXR agonist (10 mM, 24 hours). Among them, ABCA1 was one of the genes markedly induced. Real-time PCR analysis revealed that ABCA1 mRNA levels were upregulated by 2-fold in MCs. Moreover, activation of LXRs by TO901317 markedly increased the activity of ABCA1 gene promoter activity. Taken together, LXR receptors are functionally expressed in mouse mesangial cells, where their activation results in enhanced gene expression of ABCA1. The findings of these studies suggest that the LXR receptor activators may increase cholesterol efflux via induction of ABCA1 in mouse mesangial cells.