caa a22 4500 606234438 CHVBK 20210128101237.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s11010-015-2414-2 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2414-2 Inhibitory effects of peroxisome proliferator-activated receptor γ agonists on collagen IV production in podocytes [Elektronische Daten] [Yanjiao Li, Yachen Shen, Min Li, Dongming Su, Weifeng Xu, Xiubin Liang, Rongshan Li] Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have beneficial effects on the kidney diseases through preventing microalbuminuria and glomerulosclerosis. However, the mechanisms underlying these effects remain to be fully understood. In this study, we investigate the effects of PPAR-γ agonist, rosiglitazone (Rosi) and pioglitazone (Pio), on collagen IV production in mouse podocytes. The endogenous expression of PPAR-γ was found in the primary podocytes and can be upregulated by Rosi and Pio, respectively, detected by RT-PCR and Western blot. PPAR-γ agonist markedly blunted the increasing of collagen IV expression and extraction in podocytes induced by TGF-β. In contrast, adding PPAR-γ antagonist, GW9662, to podocytes largely prevented the inhibition of collagen IV expression from Pio treatment. Our data also showed that phosphorylation of Smad2/3 enhanced by TGF-β in a time-dependent manner was significantly attenuated by adding Pio. The promoter region of collagen IV gene contains one putative consensus sequence of Smad-binding element (SBE) by promoter analysis, Rosi and Pio significantly ameliorated TGF-β-induced SBE4-luciferase activity. In conclusion, PPAR-γ activation by its agonist, Rosi or Pio, in vitro directly inhibits collagen IV expression and synthesis in primary mouse podocytes. The suppression of collagen IV production was related to the inhibition of TGF-β-driven phosphorylation of Smad2/3 and decreased response activity of SBEs of collagen IV in PPAR-γ agonist-treated mouse podocytes. This represents a novel mechanistic support regarding PPAR-γ agonists as podocyte protective agents. Springer Science+Business Media New York, 2015 Podocyte nationallicence Peroxisome proliferator-activated receptor γ nationallicence Collagen IV nationallicence TGF-β nationallicence Smad-binding elements nationallicence Li Yanjiao Department of Nephrology, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, 030012, Taiyuan, Shanxi, China aut Shen Yachen Center of Metabolic Disease Research, Nanjing Medical University, 210029, Nanjing, Jiangsu, China aut Li Min Center of Metabolic Disease Research, Nanjing Medical University, 210029, Nanjing, Jiangsu, China aut Su Dongming Department of Pathology, Nanjing Medical University, 210029, Nanjing, Jiangsu, China aut Xu Weifeng Center of Metabolic Disease Research, Nanjing Medical University, 210029, Nanjing, Jiangsu, China aut Liang Xiubin Center of Metabolic Disease Research, Nanjing Medical University, 210029, Nanjing, Jiangsu, China aut Li Rongshan Department of Nephrology, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, 030012, Taiyuan, Shanxi, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 233-241 0300-8177 405:1-2<233 2015 405 11010 https://doi.org/10.1007/s11010-015-2414-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2414-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Yanjiao Department of Nephrology, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, 030012, Taiyuan, Shanxi, China aut NATIONALLICENCE 700 1- Shen Yachen Center of Metabolic Disease Research, Nanjing Medical University, 210029, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Li Min Center of Metabolic Disease Research, Nanjing Medical University, 210029, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Su Dongming Department of Pathology, Nanjing Medical University, 210029, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Xu Weifeng Center of Metabolic Disease Research, Nanjing Medical University, 210029, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Liang Xiubin Center of Metabolic Disease Research, Nanjing Medical University, 210029, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Li Rongshan Department of Nephrology, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, 030012, Taiyuan, Shanxi, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 233-241 0300-8177 405:1-2<233 2015 405 11010