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

Jill M. Ricono, Brent Wagner, Yves Gorin, Mazen Arar, Andrius Kazlauskas, Goutam Ghosh Choudhury, Hanna E. Abboud

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


PDGF B chain or PDGF receptor (PDGFR)-β-deficient (-/-) mice lack mesangial cells. To study responses of α- 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.

Original languageEnglish (US)
Pages (from-to)F406-F417
JournalAmerican Journal of Physiology - Renal Physiology
Issue number2
StatePublished - Feb 2009


  • Calcium
  • Reactive oxygen species

ASJC Scopus subject areas

  • Urology
  • Physiology


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