title: The MCP-1/CCR2 axis in podocytes is involved in apoptosis induced by diabetic conditions.
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.
authors: Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Yonsei University, Seodaemoon-Gu, Seoul, Korea.
authors: Bo Young
authors: BY
authors: Nam
authors: Jisun
authors: J
authors: Paeng
authors: Seung Hye
authors: SH
authors: Kim
authors: Sun Ha
authors: SH
authors: Lee
authors: Do Hee
authors: DH
authors: Kim
authors: Hye-Young
authors: HY
authors: Kang
authors: Jin Ji
authors: JJ
authors: Li
authors: Seung-Jae
authors: SJ
authors: Kwak
authors: Jung Tak
authors: JT
authors: Park
authors: Tae-Hyun
authors: TH
authors: Yoo
authors: Seung Hyeok
authors: SH
authors: Han
authors: Dong Ki
authors: DK
authors: Kim
authors: Shin-Wook
authors: SW
authors: Kang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050199:Podocytes / Q000166:cytology* / Q000378:metabolism; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D053773:Transforming Growth Factor beta1; D005947:Glucose