PMID- 18579703
OWN - NLM
STAT- MEDLINE
DCOM- 20081027
LR  - 20131121
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 295
IP  - 3
DP  - 2008 Sep
TI  - MCP-1/CCR2 system is involved in high glucose-induced fibronectin and type IV 
      collagen expression in cultured mesangial cells.
PG  - F749-57
LID - 10.1152/ajprenal.00547.2007 [doi]
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that plays an 
      important role in the recruitment of macrophages. Although previous studies have 
      demonstrated the importance of MCP-1 in the pathogenesis of diabetic nephropathy 
      (DN) in terms of inflammation, the role of MCP-1 and its receptor (C-C chemokine 
      receptor 2; CCR2) in extracellular matrix (ECM) accumulation under diabetic 
      conditions has been largely unexplored. This study was undertaken to investigate 
      the functional role of the MCP-1/CCR2 system in high glucose-induced ECM 
      (fibronectin and type IV collagen) protein expression in cultured mesangial cells 
      (MCs). Mouse MCs were exposed to medium containing 5.6 mM glucose (NG), NG+24.4 
      mM mannitol (NG+M), or 30 mM glucose (HG) with or without mutant MCP-1 (mMCP-1), 
      CCR2 small interfering (si)RNA, or CCR2 inhibitor (RS102895). To examine the 
      relationship between MCP-1 and transforming growth factor (TGF)-beta1, MCs were 
      also treated with TGF-beta1 (2 ng/ml) with or without mMCP-1 or CCR2 siRNA. 
      Transient transfection was performed with Lipofectamine 2000 for 24 h. Cell 
      viability was determined by an MTT assay, mouse and human MCP-1 and TGF-beta1 
      levels by ELISA, and CCR2 and ECM protein expression by Western blotting. 
      Transfections of mMCP-1 and CCR2 siRNA increased human MCP-1 levels and inhibited 
      CCR2 expression, respectively. HG-induced ECM protein expression and TGF-beta1 
      levels were significantly attenuated by mMCP-1, CCR2 siRNA, and RS102895 (P < 
      0.05). MCP-1 directly increased ECM protein expression, and this increase was 
      inhibited by an anti-TGF-beta1 antibody. In addition, TGF-beta1-induced ECM 
      protein expression was significantly abrogated by the inhibition of the 
      MCP-1/CCR2 system (P < 0.05). These results suggest that an interaction between 
      the MCP-1/CCR2 system and TGF-beta1 may contribute to ECM accumulation in DN.
FAU - Park, Jehyun
AU  - Park J
AD  - Yonsei University College of Medicine, Department of Internal Medicine, 134 
      Shinchon-Dong, Seodaemoon-Gu, Seoul, Korea.
FAU - Ryu, Dong-Ryeol
AU  - Ryu DR
FAU - Li, Jin Ji
AU  - Li JJ
FAU - Jung, Dong-Sub
AU  - Jung DS
FAU - Kwak, Seung-Jae
AU  - Kwak SJ
FAU - Lee, Sun Ha
AU  - Lee SH
FAU - Yoo, Tae-Hyun
AU  - Yoo TH
FAU - Han, Seung Hyeok
AU  - Han SH
FAU - Lee, Jung Eun
AU  - Lee JE
FAU - Kim, Dong Ki
AU  - Kim DK
FAU - Moon, Sung Jin
AU  - Moon SJ
FAU - Kim, Kunhong
AU  - Kim K
FAU - Han, Dae Suk
AU  - Han DS
FAU - Kang, Shin-Wook
AU  - Kang SW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080625
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Collagen Type IV)
RN  - 0 (Fibronectins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Transforming Growth Factor beta1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Collagen Type IV/*metabolism
MH  - Diabetic Nephropathies/metabolism
MH  - Fibronectins/*metabolism
MH  - Glucose/metabolism
MH  - Humans
MH  - Mesangial Cells/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutation
MH  - RNA, Small Interfering/genetics
MH  - Receptors, CCR2/genetics/*metabolism
MH  - Transfection
MH  - Transforming Growth Factor beta1/metabolism
EDAT- 2008/06/27 09:00
MHDA- 2008/10/28 09:00
CRDT- 2008/06/27 09:00
PHST- 2008/06/27 09:00 [pubmed]
PHST- 2008/10/28 09:00 [medline]
PHST- 2008/06/27 09:00 [entrez]
AID - 00547.2007 [pii]
AID - 10.1152/ajprenal.00547.2007 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2008 Sep;295(3):F749-57. doi: 
      10.1152/ajprenal.00547.2007. Epub 2008 Jun 25.