PMID- 19587356
OWN - NLM
STAT- MEDLINE
DCOM- 20090930
LR  - 20220330
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 58
IP  - 9
DP  - 2009 Sep
TI  - Effect of the monocyte chemoattractant protein-1/CC chemokine receptor 2 system 
      on nephrin expression in streptozotocin-treated mice and human cultured 
      podocytes.
PG  - 2109-18
LID - 10.2337/db08-0895 [doi]
AB  - OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1), a chemokine binding to the 
      CC chemokine receptor 2 (CCR2) and promoting monocyte infiltration, has been 
      implicated in the pathogenesis of diabetic nephropathy. To assess the potential 
      relevance of the MCP-1/CCR2 system in the pathogenesis of diabetic proteinuria, 
      we studied in vitro if MCP-1 binding to the CCR2 receptor modulates nephrin 
      expression in cultured podocytes. Moreover, we investigated in vivo if glomerular 
      CCR2 expression is altered in kidney biopsies from patients with diabetic 
      nephropathy and whether lack of MCP-1 affects proteinuria and expression of 
      nephrin in experimental diabetes. RESEARCH DESIGN AND METHODS: Expression of 
      nephrin was assessed in human podocytes exposed to rh-MCP-1 by immunofluorescence 
      and real-time PCR. Glomerular CCR2 expression was studied in 10 kidney sections 
      from patients with overt nephropathy and eight control subjects by 
      immunohistochemistry. Both wild-type and MCP-1 knockout mice were made diabetic 
      with streptozotocin. Ten weeks after the onset of diabetes, albuminuria and 
      expression of nephrin, synaptopodin, and zonula occludens-1 were examined by 
      immunofluorescence and immunoblotting. RESULTS: In human podocytes, MCP-1 binding 
      to the CCR2 receptor induced a significant reduction in nephrin both mRNA and 
      protein expression via a Rho-dependent mechanism. The MCP-1 receptor, CCR2, was 
      overexpressed in the glomerular podocytes of patients with overt nephropathy. In 
      experimental diabetes, MCP-1 was overexpressed within the glomeruli and the 
      absence of MCP-1 reduced both albuminuria and downregulation of nephrin and 
      synaptopodin. CONCLUSIONS: These findings suggest that the MCP-1/CCR2 system may 
      be relevant in the pathogenesis of proteinuria in diabetes.
FAU - Tarabra, Elena
AU  - Tarabra E
AD  - Diabetic Nephropathy Laboratory, Department of Internal Medicine, University of 
      Turin, Italy.
FAU - Giunti, Sara
AU  - Giunti S
FAU - Barutta, Federica
AU  - Barutta F
FAU - Salvidio, Gennaro
AU  - Salvidio G
FAU - Burt, Davina
AU  - Burt D
FAU - Deferrari, Giacomo
AU  - Deferrari G
FAU - Gambino, Roberto
AU  - Gambino R
FAU - Vergola, Daniela
AU  - Vergola D
FAU - Pinach, Silvia
AU  - Pinach S
FAU - Perin, Paolo Cavallo
AU  - Perin PC
FAU - Camussi, Giovanni
AU  - Camussi G
FAU - Gruden, Gabriella
AU  - Gruden G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090708
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (CCL2 protein, human)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Membrane Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (SYNPO protein, human)
RN  - 0 (TJP1 protein, human)
RN  - 0 (Tjp1 protein, mouse)
RN  - 0 (Zonula Occludens-1 Protein)
RN  - 0 (nephrin)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Animals
MH  - Biopsy
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism/pharmacology
MH  - Diabetes Mellitus, Experimental/metabolism/pathology/*physiopathology
MH  - Diabetic Nephropathies/metabolism/pathology/*physiopathology
MH  - Down-Regulation/physiology
MH  - Humans
MH  - In Vitro Techniques
MH  - Membrane Proteins/*genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microfilament Proteins/metabolism
MH  - Phosphoproteins/metabolism
MH  - Podocytes/cytology/*physiology
MH  - Proteinuria/metabolism/pathology/physiopathology
MH  - RNA, Messenger/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Zonula Occludens-1 Protein
MH  - rho-Associated Kinases/metabolism
PMC - PMC2731530
EDAT- 2009/07/10 09:00
MHDA- 2009/10/01 06:00
PMCR- 2010/09/01
CRDT- 2009/07/10 09:00
PHST- 2009/07/10 09:00 [entrez]
PHST- 2009/07/10 09:00 [pubmed]
PHST- 2009/10/01 06:00 [medline]
PHST- 2010/09/01 00:00 [pmc-release]
AID - db08-0895 [pii]
AID - 0895 [pii]
AID - 10.2337/db08-0895 [doi]
PST - ppublish
SO  - Diabetes. 2009 Sep;58(9):2109-18. doi: 10.2337/db08-0895. Epub 2009 Jul 8.