PMID- 22006533
OWN - NLM
STAT- MEDLINE
DCOM- 20120507
LR  - 20160721
IS  - 1573-675X (Electronic)
IS  - 1360-8185 (Linking)
VI  - 17
IP  - 1
DP  - 2012 Jan
TI  - The MCP-1/CCR2 axis in podocytes is involved in apoptosis induced by diabetic 
      conditions.
PG  - 1-13
LID - 10.1007/s10495-011-0661-6 [doi]
AB  - 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-beta1 with 
      or without anti-TGF-beta1 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-beta1 levels were 
      significantly abrogated by CCR2 inhibition. In addition, treatment with MCP-1 
      directly induced apoptosis via CCR2. Moreover, TGF-beta1- and MCP-1-induced 
      apoptosis were significantly ameliorated by the inhibition of CCR2 and 
      anti-TGF-beta1 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-beta1 may contribute to podocyte apoptosis under diabetic 
      conditions.
FAU - Nam, Bo Young
AU  - Nam BY
AD  - Department of Internal Medicine, College of Medicine, Severance Biomedical 
      Science Institute, Yonsei University, Seodaemoon-Gu, Seoul, Korea.
FAU - Paeng, Jisun
AU  - Paeng J
FAU - Kim, Seung Hye
AU  - Kim SH
FAU - Lee, Sun Ha
AU  - Lee SH
FAU - Kim, Do Hee
AU  - Kim DH
FAU - Kang, Hye-Young
AU  - Kang HY
FAU - Li, Jin Ji
AU  - Li JJ
FAU - Kwak, Seung-Jae
AU  - Kwak SJ
FAU - Park, Jung Tak
AU  - Park JT
FAU - Yoo, Tae-Hyun
AU  - Yoo TH
FAU - Han, Seung Hyeok
AU  - Han SH
FAU - Kim, Dong Ki
AU  - Kim DK
FAU - Kang, Shin-Wook
AU  - Kang SW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Transforming Growth Factor beta1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Diabetic Nephropathies/genetics/metabolism/*physiopathology
MH  - Disease Models, Animal
MH  - Female
MH  - Glucose
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Podocytes/*cytology/metabolism
MH  - Receptors, CCR2/genetics/*metabolism
MH  - Transforming Growth Factor beta1/metabolism
EDAT- 2011/10/19 06:00
MHDA- 2012/05/09 06:00
CRDT- 2011/10/19 06:00
PHST- 2011/10/19 06:00 [entrez]
PHST- 2011/10/19 06:00 [pubmed]
PHST- 2012/05/09 06:00 [medline]
AID - 10.1007/s10495-011-0661-6 [doi]
PST - ppublish
SO  - Apoptosis. 2012 Jan;17(1):1-13. doi: 10.1007/s10495-011-0661-6.