Over-expression of Liver X Receptor-alpha(LXR alpha by TO901317 Exaggerated the Production of Mesangial Matrix / 대한신장학회지

ABSTRACT

PURPOSE: To provide the insight into the role of LXR alpha on the progression of diabetic nephropathy, we measured the production of extracellular matrix in the cultured mesangial cells treated with the LXR agonist. METHODS: With the mesangial cells extracted from C57BL6 mice, we cultured them in the presence of 25 mM glucose with or without TO901317, an agonist of LXRalpha We transfected siRNAs of SREBP1 and LXR alpha into the mesangial cell to suppress the activity of the two genes. RESULTS: TO901317 increased expressions of LXR alpha, SREBP-1, TGF beta-1, and collagen IV and triglyceride amount in mesangial cells cultured in 25mM glucose. These effects of TO901317 were attenuated by inhibiting transcription of LXR alpha or SREBP-1 with transfection of siRNAs. In mesangial cells transfected with siRNA of SREBP-1, changes by TO901317 were attenuated regardless of increased expression of LXR alpha. That suggested the activation of SREBP-1, an downstream gene of LXR alpha, would be more important to induce changes in mesangial cells by TO901317. CONCLUSION: The TO901317, an agonist of LXR alpha, increases extracellular matrix, collagen IV, and TGF beta-1 production in cultured mesangial cells. The SREBP-1 as well as dyslipidemia in mesangial cells enhanced by LXR agonist would be the important mechanism to induce those changes.