Over-expression of Liver X Receptor- α (LXRα) by TO901317 Exaggerated the Production of Mesangial Matrix

Korean Journal of Nephrology 2010;29(2):189-197.

Ho Jun Chin, M.D., Ph.D,1, 2, 3, Yan Yan Fu, M.D.2, Young Rim Song, M.D.4, En Sung Lee2, Yun Mi Lee2, Seong Gyun Kim, M.D., Ph.D.4, Ki Young Na, M.D., Ph.D.1, 2, Suhnggwon Kim, M.D., Ph.D.1, 3 and Dong-Wan Chae, M.D., Ph.D.1, 2, 3

Department of Internal Medicine¹
Seoul National University College of Medicine, Department of Internal Medicine²
Seoul National University Bundang Hospital Renal Research Institute³
Seoul National University College of Medicine, Department of Internal Medicine⁴
Hallym University College of Medicine

원저 : Over-expression of Liver X Receptor- α (LXRα) by TO901317 Exaggerated the Production of Mesangial Matrix

Department of Internal Medicine1, Seoul National University College of Medicine, Department of Internal Medicine2, Seoul National University Bundang Hospital Renal Research Institute3, Seoul National University College of Medicine, Department of Internal

Abstract

Purpose : To provide the insight into the role of LXRα 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 LXRα. We transfected siRNAs of SREBP1 and LXRα into the mesangial cell to suppress the activity of the two genes. Results : TO901317 increased expressions of LXRα, SREBP-1, TGFβ-1, and collagen IV and triglyceride amount in mesangial cells cultured in 25mM glucose. These effects of TO901317 were attenuated by inhibiting transcription of LXRα 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 LXRα. That suggested the activation of SREBP-1, an downstream gene of LXRα, would be more important to induce changes in mesangial cells by TO901317. Conclusion : The TO901317, an agonist of LXRα, increases extracellular matrix, collagen IV, and TGF β-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.

Key Words: Diabetic nephropathies, Hypertriglyceridemia, Liver X receptor, Sterol regulatory element binding pr