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This Article Full Text Full Text (PDF) All Versions of this Article: 296/2/F406    most recent 90368.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ricono, J. M. Articles by Abboud, H. E. Search for Related Content PubMed PubMed Citation Articles by Ricono, J. M. Articles by Abboud, H. E.

PDGF receptor-β modulates metanephric mesenchyme chemotaxis induced by PDGF AA

¹Department of Molecular Medicine, Institute of Biotechnology, Departments of ²Medicine and ⁴Pediatrics, University of Texas Health Science Center, and ³South Texas Veterans Health Care System/Audie L. Murphy Memorial Hospital Division, San Antonio, Texas; and ⁵Schepens Eye Institute, Harvard Medical School, Boston, Massachusetts

Submitted 13 June 2008 ; accepted in final form 18 November 2008

PDGF B chain or PDGF receptor (PDGFR)-β-deficient (–/–) mice lack mesangial cells. To study responses of - and β-receptor activation to PDGF ligands, metanephric mesenchymal cells (MMCs) were established from embryonic day E11.5 wild-type (+/+) and –/– mouse embryos. PDGF BB stimulated cell migration in +/+ cells, whereas PDGF AA did not. Conversely, PDGF AA was chemotactic for –/– MMCs. The mechanism by which PDGFR-β inhibited AA-induced migration was investigated. PDGF BB, but not PDGF AA, increased intracellular Ca²⁺ and the production of reactive oxygen species (ROS) in +/+ cells. Transfection of –/– MMCs with the wild-type β-receptor restored cell migration and ROS generation in response to PDGF BB and inhibited AA-induced migration. Inhibition of Ca²⁺ signaling facilitated PDGF AA-induced chemotaxis in the wild-type cells. The antioxidant N-acetyl-L-cysteine (NAC) or the NADPH oxidase inhibitor diphenyleneiodonium (DPI) abolished the BB-induced increase in intracellular Ca²⁺ concentration, suggesting that ROS act as upstream mediators of Ca²⁺ in suppressing PDGF AA-induced migration. These data indicate that ROS and Ca²⁺ generated by active PDGFR-β play an essential role in suppressing PDGF AA-induced migration in +/+ MMCs. During kidney development, PDGFR β-mediated ROS generation and Ca²⁺ influx suppress PDGF AA-induced chemotaxis in metanephric mesenchyme.

reactive oxygen species; calcium