PPARy agonists inhibit TGF-β-PKA signaling in glomeru Iosclerosis  

作　　者：Rong ZOU Gang XU Xiao-cheng LIU Min HAN Jing-jing JIANG Qian HUANG Yong HE Ying YAO 

机构地区：[1]Department of Nephrology, Tongli Hospital, Tongli Medical College, Huazhong University of Science and Technology, Wuhan 430030,China [2]Department of Nephrology, Wuhan Integrated TCM & Western Medicine Hospital, Tongti Medical College, Huazhong Universityof Science and Technology, Wuhan 430030, China

出　　处：《Acta Pharmacologica Sinica》2010年第1期43-50,共8页中国药理学报（英文版）

基　　金：This project was supported by the National Natural Science Foundation of China （No 30672227; 30571950; 30600667; 30700895; 30628029; 30770913）.

摘　　要：Aim： To study the probable mechanisms of the anti-glomerulosclerosis effects induced by peroxisome proliferator-activated receptor gamma （PPARy） agonists in rat intraglomerular mesangial cells （MCs）. Methods： Cells were transfected with the pTAL-PPRE-tk-Luc plasmid and then treated with different concentrations of PPARy agonist, either troglitazone or telmisartan, for the indicated times. Promega luciferase assays were subsequently used for the detection of PPARy activation. Protein expression levels were assessed by Western blot, and PepTag assays were used for the non-radioactive detection of protein kinase A （PKA） activity. The deposition of （x-smooth muscle actin （（x-SMA） and p-cyclic AMP responsive element binding protein （pCREB） were analyzed by confocal laser scanning. Results： Both troglitazone and telmisartan remarkably inhibit the PKA activation and pCREB expression that is stimulated by TGF-β, The PPARy agonists also inhibited α-SMA and collagen IV protein expression by blocking PKA activation. Conclusion： PPARy ligands effectively suppress the activation of MCs and the accumulation of collagen IV stimulated by TGF-β in vitro. The renal protection provided by PPARy agonists is partly mediated via their blockade of TGF-β/PKA signaling.Aim： To study the probable mechanisms of the anti-glomerulosclerosis effects induced by peroxisome proliferator-activated receptor gamma （PPARy） agonists in rat intraglomerular mesangial cells （MCs）. Methods： Cells were transfected with the pTAL-PPRE-tk-Luc plasmid and then treated with different concentrations of PPARy agonist, either troglitazone or telmisartan, for the indicated times. Promega luciferase assays were subsequently used for the detection of PPARy activation. Protein expression levels were assessed by Western blot, and PepTag assays were used for the non-radioactive detection of protein kinase A （PKA） activity. The deposition of （x-smooth muscle actin （（x-SMA） and p-cyclic AMP responsive element binding protein （pCREB） were analyzed by confocal laser scanning. Results： Both troglitazone and telmisartan remarkably inhibit the PKA activation and pCREB expression that is stimulated by TGF-β, The PPARy agonists also inhibited α-SMA and collagen IV protein expression by blocking PKA activation. Conclusion： PPARy ligands effectively suppress the activation of MCs and the accumulation of collagen IV stimulated by TGF-β in vitro. The renal protection provided by PPARy agonists is partly mediated via their blockade of TGF-β/PKA signaling.

关 键 词：PKA signal pathway GLOMERULOSCLEROSIS PPARY rat intraglomerular mesangial cells TROGLITAZONE TELMISARTAN 

分 类 号：Q26[生物学—细胞生物学] Q279