Abstract | OBJECTIVE: 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.
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Authors | Elena Tarabra, Sara Giunti, Federica Barutta, Gennaro Salvidio, Davina Burt, Giacomo Deferrari, Roberto Gambino, Daniela Vergola, Silvia Pinach, Paolo Cavallo Perin, Giovanni Camussi, Gabriella Gruden |
Journal | Diabetes
(Diabetes)
Vol. 58
Issue 9
Pg. 2109-18
(Sep 2009)
ISSN: 1939-327X [Electronic] United States |
PMID | 19587356
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CCL2 protein, human
- Ccl2 protein, mouse
- Chemokine CCL2
- Membrane Proteins
- Microfilament Proteins
- Phosphoproteins
- RNA, Messenger
- Recombinant Proteins
- SYNPO protein, human
- TJP1 protein, human
- Tjp1 protein, mouse
- Zonula Occludens-1 Protein
- nephrin
- rho-Associated Kinases
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Topics |
- Animals
- Biopsy
- Cells, Cultured
- Chemokine CCL2
(genetics, metabolism, pharmacology)
- Diabetes Mellitus, Experimental
(metabolism, pathology, physiopathology)
- Diabetic Nephropathies
(metabolism, pathology, physiopathology)
- Down-Regulation
(physiology)
- Humans
- In Vitro Techniques
- Membrane Proteins
(genetics, metabolism)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Microfilament Proteins
(metabolism)
- Phosphoproteins
(metabolism)
- Podocytes
(cytology, physiology)
- Proteinuria
(metabolism, pathology, physiopathology)
- RNA, Messenger
(metabolism)
- Recombinant Proteins
(pharmacology)
- Zonula Occludens-1 Protein
- rho-Associated Kinases
(metabolism)
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