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Interleukin-10 expression induced by adeno-associated virus vector suppresses proteinuria in Zucker obese rats

Gene Therapy volume 19, pages 476–482 (2012)Cite this article

Abstract

Varying degrees of metabolic abnormalities mediated by chronic inflammation are implicated in the chronic glomerular injuries associated with obesity. Interleukin (IL)-10, a pleiotropic cytokine, exerts anti-inflammatory effects in numerous biological settings. In the present study, we explored the biological benefits of adeno-associated virus (AAV) vector-mediated sustained IL-10 expression against the pathological renal characteristics observed in Zucker fatty rats (ZFRs). We injected an AAV vector, encoding rat IL-10 or enhanced green fluorescent protein (GFP) into male ZFRs at 5 weeks of age. Subsequently, the renal pathophysiological changes were analyzed. Persistent IL-10 expression significantly reduced the urinary protein excretion of ZFRs compared with GFP expression (47.1±11.6 mg per mg·creatinine versus 88.8±30.0 mg per mg·creatinine, P<0.01). The serum levels of IL-10 negatively correlated with the urinary protein in AAV-treated rats (r=−0.78, P<0.01). Renal hypertrophy, increased widths in the glomerular basement membrane, and the lack of uniformity and regularity of the foot process of the visceral glomerular epithelial cells of ZFRs were significantly blunted by IL-10 expression. IL-10 also abrogated the downregulation of glomerular nephrin observed in ZFRs treated with the GFP vector. Our findings provide insights into the potential benefit of the anti-inflammatory effects of IL-10 on the overall management of glomerulopathy induced by the metabolic disorders associated with obesity.

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Acknowledgements

Part of the work presented in the original manuscript was presented in abstract in the Renal Week 2009 (Annual Meeting of the American Society of Nephrology). We sincerely thank Takashi Yashiro for conducting the electron microscopy studies, and Tom Kouki for his technical assistance in tissue processing for histological and ultrastructural studies.

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Authors and Affiliations

  1. Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan

    M Ogura, M Urabe, A Onishi, T Tsukahara, H Mizukami, A Kume & K Ozawa

  2. Division of Nephrology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan

    M Ogura, T Akimoto, A Onishi, C Ito, S Muto & E Kusano

  3. Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University, Shimotsuke, Japan

    T Ito

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  1. M Ogura
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Correspondence to M Ogura.

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Ogura, M., Urabe, M., Akimoto, T. et al. Interleukin-10 expression induced by adeno-associated virus vector suppresses proteinuria in Zucker obese rats. Gene Ther 19, 476–482 (2012). https://doi.org/10.1038/gt.2011.183

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