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

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, Dong Ki Kim, Shin Wook Kang

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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.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalApoptosis
Volume17
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

Cite this

Nam, B. Y., Paeng, J., Kim, S. H., Lee, S. H., Kim, D. H., Kang, H. Y., Li, J. J., Kwak, S. J., Park, J. T., Yoo, T. H., Han, S. H., Kim, D. K., & Kang, S. W. (2012). The MCP-1/CCR2 axis in podocytes is involved in apoptosis induced by diabetic conditions. Apoptosis, 17(1), 1-13. https://doi.org/10.1007/s10495-011-0661-6