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The MCP-1/CCR2 axis in podocytes is involved in apoptosis induced by diabetic conditions

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Abstract

Previous studies have demonstrated the importance of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of diabetic nephropathy in terms of inflammation, but the direct role of the MCP-1/CCR2 system on podocyte apoptosis under diabetic conditions has never been explored. In vitro, mouse podocytes were exposed to a medium containing 30 mM glucose (HG) with or without CCR2 siRNA or CCR2 inhibitor (RS102895). Podocytes were also treated with MCP-1 or TGF-β1 with or without anti-TGF-β1 antibody, CCR2 siRNA, or CCR2 inhibitor. In vivo, 20 db/m and 20 db/db mice were divided into two groups, and ten mice from each group were treated with RS102895. Western blot and Hoechst 33342 or TUNEL staining were performed to identify apoptosis. HG-induced apoptosis and TGF-β1 levels were significantly abrogated by CCR2 inhibition. In addition, treatment with MCP-1 directly induced apoptosis via CCR2. Moreover, TGF-β1- and MCP-1-induced apoptosis were significantly ameliorated by the inhibition of CCR2 and anti-TGF-β1 antibody, respectively. Glomerular expression of cleaved caspase-3 and apoptotic cells within glomeruli were also significantly increased in db/db mice compared to db/m mice, and these increases were significantly attenuated in db/db + RS102895 mice. These results suggest that interactions between the MCP-1/CCR2 system and TGF-β1 may contribute to podocyte apoptosis under diabetic conditions.

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Acknowledgments

This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2009-0089803), the BK21 (Brain Korea 21) Project for Medical Sciences, Yonsei University, and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0030711).

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None declared.

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Authors and Affiliations

  1. Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, BK21, Yonsei University, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul, 120-752, Korea

    Bo Young Nam, Jisun Paeng, Seung Hye Kim, Sun Ha Lee, Do Hee Kim, Hye-Young Kang, Jin Ji Li, Seung-Jae Kwak, Jung Tak Park, Tae-Hyun Yoo, Seung Hyeok Han & Shin-Wook Kang

  2. Nephrology and Dialysis Unit, Department of Internal Medicine, The Affiliated Hospital, YanBian University Medical College, JiLin, China

    Jin Ji Li

  3. Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

    Dong Ki Kim

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  1. Bo Young Nam
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Correspondence to Shin-Wook Kang.

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B.Y. Nam, J. Paeng, and S.H. Kim are contributed equally to this work.

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Nam, B.Y., Paeng, J., Kim, S.H. et al. The MCP-1/CCR2 axis in podocytes is involved in apoptosis induced by diabetic conditions. Apoptosis 17, 1–13 (2012). https://doi.org/10.1007/s10495-011-0661-6

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