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Inhibitory effects of peroxisome proliferator-activated receptor γ agonists on collagen IV production in podocytes

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Abstract

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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China Grant 31071026, 31271263, 81470040 to X. Liang, 81450033 to R. Li; National Science and Technology Support Program, China (2011BAI0B01) and International Cooperative Program of Shanxi Province, China (2014081054) to R. Li.

Conflict of interest

No conflicts of interest, financial or otherwise, are declared by the authors.

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Authors and Affiliations

  1. Department of Nephrology, Shanxi Provincial People’s Hospital, The Affiliated People’s Hospital of Shanxi Medical University, Taiyuan, 030012, Shanxi, China

    Yanjiao Li & Rongshan Li

  2. Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Yanjiao Li

  3. Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, 210029, Jiangsu, China

    Yachen Shen, Min Li, Weifeng Xu & Xiubin Liang

  4. Department of Pathology, Nanjing Medical University, Nanjing, 210029, Jiangsu, China

    Dongming Su

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  1. Yanjiao Li
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  2. Yachen Shen
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  4. Dongming Su
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Correspondence to Xiubin Liang or Rongshan Li.

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Li, Y., Shen, Y., Li, M. et al. Inhibitory effects of peroxisome proliferator-activated receptor γ agonists on collagen IV production in podocytes. Mol Cell Biochem 405, 233–241 (2015). https://doi.org/10.1007/s11010-015-2414-2

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