Liver X Receptors Mediate Cholesterol Efflux In Mouse Glomerular Mesangial Cells

Glomerulosclerosis is a common pathophysiological process in chronic renal disease and is a risk factor for the progression of renal damage. Increasing evidence suggests that lipid metabolism plays an important role in the pathogenesis of glomerulosclerosis. Clinical studies indicate that correction of dyslipidemia frequently associated with renal disease may slow the progression of chronic renal failure. Thus, elucidation of the mechanisms by which dyslipidemia worsen glomerulosclerosis may help in developing novel therapeutic option for the treatment of glomerulosclerosis. Mesangial cells are phenotypically similar to vascular smooth muscle cells and macrophages. Lipid accumulation in mesangial cells have been found to lead to foam cell formation and glomerulosclerosis, suggesting mesangial cells play an important role in glomerular lipid homeostasis.Liver X receptors (LXRs) are members of the nuclear receptor superfamily and exist in two isoforms including LXRα and LXRβ. LXRs, which are activated by endogenous (oxysterol) or synthetic ligands (TO901317), bind to a characteristic DNA sequence designated LXRE via forming a heterodimer with the retinoid X receptor α (RXRα). LXRs function as sterol sensors and enhance transcription of an array of genes...