吳寬墩2006-07-262018-07-112006-07-262018-07-112003http://ntur.lib.ntu.edu.tw//handle/246246/23609Background. Glomerulosclerosis is a central pathologic feature of progressive renal diseases. Mesangial cell proliferation and extracellular matrix (ECM) deposition are regarded as main processes predisposing to glomerulosclerosis. The peroxisome proliferator-activated receptor γ (PPAR γ ) is a member of nuclear receptor superfamily that regulates fat-cell differentiation and glucose homeostasis and is the molecular target of a class of insulin-sensitizing agents used for the management of type II diabetes mellitus. Thiazolidinedione (TZD), a synthetic ligand of PPAR γ ,was shown to ameliorate mesangial expansion in vivo. Thus, we investigated the effect of PPAR γ ligands in inhibiting cell proliferation and ECM gene expression of rat mesangial cells (RMCs) in vitro. Methods. RMCs were cultured from Sprague-Dawley rats by a modified enzyme digestion method. Cell proliferation was measured by the methyltetrazolium assay. Cell-cycle distribution of RMC was analyzed by flow cytometry. Expression of type I (α 1) collagen, fibronectin and connective tissue growth factor (CTGF) mRNA level were analyzed by Northern blotting. Results. Treatment of cultured-RMCs with ligands for PPAR γ: [rosiglitazone (RSG), 1 ~50 µM or 15-deoxy-delta 12, 14 -prostaglandin J2 (15d-PGJ2), 1 ~10 µM] inhibited serum and platelet-derived growth factor (PDGF)-stimulated RMCs proliferation without affecting the cell viability. The PPAR γ activation suppressed PDGF-stimulated RMCs proliferation by cell-cycle arrest at the G1 phase. PPAR agonists suppressed serum and transforming growth factor-β (TGF-β )-induced extracellular matrix gene and CTGF gene expression in RMCs cultures. Conclusions. PPAR γ ligands, RSG and 15d-PGJ2, inhibit RMC proliferation, type I (α 1) collagen, fibronectin and CTGF mRNA expression. These results indicate that PPAR γ ligands have therapeutic potential in progressive renal disease.application/pdf331103 bytesapplication/pdfzh-TW國立臺灣大學醫學院內科PPAR γ大鼠腎膈細胞細胞週期細胞增生細胞外間質結締組織生長因子腎小球硬化症peroxisome proliferator-activated receptor γrat mesangial cellcell proliferationcell cycleextracellular matrixconnective tissue growth factorglomeruloscleroris[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/23609/1/912314B002336.pdf