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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 
Journal Title
Issue Date
Animals ; Apoptosis* ; Cells, Cultured ; Chemokine CCL2/genetics ; Chemokine CCL2/metabolism* ; Diabetic Nephropathies/genetics ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/physiopathology* ; Disease Models, Animal ; Female ; Glucose ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Podocytes/cytology* ; Podocytes/metabolism ; Receptors, CCR2/genetics ; Receptors, CCR2/metabolism* ; Transforming Growth Factor beta1/metabolism
Diabetic nephropathy ; Podocytes ; Monocyte chemoattractant protein-1 ; Transforming growth factor-β1 ; Apoptosis
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. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kang, Hye Young(강혜영)
Kwak, Seung Jae(곽승재)
Kim, Seung Hye(김승혜)
Nam, Bo Young(남보영)
Park, Jung Tak(박정탁) ORCID logo https://orcid.org/0000-0002-2325-8982
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Lee, Sun Ha(이순하)
Paeng, Ji Sun(팽지선)
Han, Seung Hyeok(한승혁) ORCID logo https://orcid.org/0000-0001-7923-5635
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