ELR+-CXC chemokines and their receptors in early metanephric development.

Authors: Levashova, ZB  Sharma, N  Timofeeva, OA  Dome, JS  Perantoni, AO 
Citation: Levashova ZB, etal., J Am Soc Nephrol. 2007 Aug;18(8):2359-70. Epub 2007 Jul 18.
Pubmed: (View Article at PubMed) PMID:17634442
DOI: Full-text: DOI:10.1681/ASN.2006040380

Although originally identified as mediators of inflammation, it is now apparent that chemokines play a fundamental role in tissue development. In this study, ELR(+)-CXC chemokine family members CXCL2 and CXCL7, along with their preferred receptor CXCR2, were expressed at the earliest stages of metanephric development in the rat, and signaling through this receptor was required for the survival and maintenance of the undifferentiated metanephric mesenchyme (MM). A specific antagonist of the CXCR2 receptor SB225002 induced apoptosis in this population but did not affect more mature structures or cells in the ureteric bud. CXCL7 treatment of isolated MM elicited an angiogenic response by upregulation of matrix metalloprotease 9 and endothelial and mesangial markers (platelet-endothelial cell adhesion molecule, Megsin, Thy-1, PDGF receptor alpha, and vascular alpha-actin) and induced SB225002-sensitive cell invasion through a matrix. Because Wilms' tumor cells may similarly depend on CXCR2 signaling for survival, primary tumor samples were analyzed, and 15 of 16 Wilms' tumors were found to be CXCR2 positive, whereas grossly normal kidney tissues from tumor patients or renal cell carcinomas were CXCR2 negative. Furthermore, cell lines derived from Wilms' tumors but not those from renal cell carcinomas were sensitive to SB225002-induced apoptosis. These data provide evidence for a prosurvival and proangiogenic role of ELR(+)-CXC chemokines and their receptor CXCR2 during metanephric development and suggest a novel mechanism for chemotherapeutic intervention in Wilms' tumor.

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CRRD Object Information
CRRD ID: 7257700
Created: 2013-08-30
Species: All species
Last Modified: 2013-08-30
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.