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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 
 Apoptosis, Vol.17(1) : 1-13, 2012 
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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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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
Yonsei Authors
강신욱(Kang, Shin Wook) ORCID logo https://orcid.org/0000-0002-5677-4756
강혜영(Kang, Hye Young)
곽승재(Kwak, Seung Jae)
김승혜(Kim, Seung Hye)
남보영(Nam, Bo Young)
박정탁(Park, Jung Tak) ORCID logo https://orcid.org/0000-0002-2325-8982
유태현(Yoo, Tae Hyun) ORCID logo https://orcid.org/0000-0002-9183-4507
이순하(Lee, Sun Ha)
팽지선(Paeng, Ji Sun)
한승혁(Han, Seung Hyeok) ORCID logo https://orcid.org/0000-0001-7923-5635
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