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Originally published online as doi:10.2353/ajpath.2007.070398 on November 30, 2007

Published online before print November 30, 2007
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(American Journal of Pathology. 2007;171:1789-1799.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.070398

The Monocyte Chemoattractant Protein-1/Cognate CC Chemokine Receptor 2 System Affects Cell Motility in Cultured Human Podocytes

Davina Burt*, Gennaro Salvidio{dagger}, Elena Tarabra*, Federica Barutta*, Silvia Pinach*, Patrizia Dentelli*, Giovanni Camussi*, Paolo Cavallo Perin* and Gabriella Gruden*

From the Department of Internal Medicine,* University of Turin, Turin; and the Department of Cardionephrology,{dagger} University of Genoa, Genoa, Italy

In crescentic glomerulonephritis (GN), monocyte chemoattractant protein-1 (MCP-1) is overexpressed within the glomeruli, and MCP-1 blockade has renoprotective effects. Adult podocytes are in a quiescent state, but acquisition of a migratory/proliferative phenotype has been described in crescentic GN and implicated in crescent formation. The cognate CC chemokine receptor 2 (CCR2), the MCP-1 receptor, is expressed by other cell types besides monocytes and has been implicated in both cell proliferation and migration. We investigated whether MCP-1 binding to CCR2 can induce a migratory/proliferative response in cultured podocytes. MCP-1 binding to CCR2 enhanced podocyte chemotaxis/haptotaxis in a concentration-dependent manner and had a modest effect on cell proliferation. Closure of a wounded podocyte monolayer was delayed by CCR2 blockade, and CCR2 was overexpressed at the wound edge, suggesting a role for CCR2 in driving podocyte migration. Immunohistochemical analysis of kidney biopsies from patients with crescentic GN demonstrated CCR2 expression in both podocytes and cellular crescents, confirming the clinical relevance of our in vitro findings. In conclusion, the MCP-1/CCR2 system is functionally active in podocytes and may be implicated in the migratory events triggered by podocyte injury in crescentic GN and other glomerular diseases.




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