PMID- 18055544 OWN - NLM STAT- MEDLINE DCOM- 20080208 LR - 20211020 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 171 IP - 6 DP - 2007 Dec TI - The monocyte chemoattractant protein-1/cognate CC chemokine receptor 2 system affects cell motility in cultured human podocytes. PG - 1789-99 AB - 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. FAU - Burt, Davina AU - Burt D AD - Diabetic Nephropathy Laboratory, Department of Internal Medicine, University of Turin, Turin, 10126, Italy. davina.burt@unito.it FAU - Salvidio, Gennaro AU - Salvidio G FAU - Tarabra, Elena AU - Tarabra E FAU - Barutta, Federica AU - Barutta F FAU - Pinach, Silvia AU - Pinach S FAU - Dentelli, Patrizia AU - Dentelli P FAU - Camussi, Giovanni AU - Camussi G FAU - Perin, Paolo Cavallo AU - Perin PC FAU - Gruden, Gabriella AU - Gruden G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071130 PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Chemokine CCL2) RN - 0 (Membrane Proteins) RN - 0 (Receptors, CCR2) RN - 0 (nephrin) SB - IM MH - Cell Movement MH - Cells, Cultured MH - Chemokine CCL2/*metabolism/pharmacology MH - *Chemotaxis MH - Glomerulonephritis/metabolism/*pathology MH - Humans MH - Kidney/chemistry/metabolism/pathology MH - Membrane Proteins/metabolism MH - Podocytes/drug effects/metabolism/*pathology MH - Receptors, CCR2/analysis/*metabolism PMC - PMC2111103 EDAT- 2007/12/07 09:00 MHDA- 2008/02/09 09:00 PMCR- 2008/06/01 CRDT- 2007/12/07 09:00 PHST- 2007/12/07 09:00 [pubmed] PHST- 2008/02/09 09:00 [medline] PHST- 2007/12/07 09:00 [entrez] PHST- 2008/06/01 00:00 [pmc-release] AID - S0002-9440(10)62441-8 [pii] AID - 10.2353/ajpath.2007.070398 [doi] PST - ppublish SO - Am J Pathol. 2007 Dec;171(6):1789-99. doi: 10.2353/ajpath.2007.070398. Epub 2007 Nov 30.