Submitted on June 13, 2008
Revised on October 8, 2008
Accepted on November 18, 2008
PDGF Receptor 
modulates metanephric mesenchyme chemotaxis induced by PDGF AA
Jill M. Ricono1, Brent Wagner2*, Yves C Gorin2, Mazen Arar3, Andrius Kazlauskas4, Goutam Ghosh Choudjury5, and Hanna E. Abboud2
1 Institute of Biotechnology
2 University of Texas Health Science Center at San Antonio
3 University of Texas Health Science Center
4 Harvard Medical School
5 South Texas Veterans Health Care System/Audie L. Murphy Memorial Hospital Division
* To whom correspondence should be addressed. E-mail: wagnerb{at}uthscsa.edu.
PDGF B chain or PDGF receptor (PDGFR) 
-deficient (-/-) mice lack mesangial cells. To study responses of 
and receptor activation to PDGF ligands, metanephric mesenchymal cells (MMCs) were established from 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 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 receptor restored cell migration and ROS generation in response to PDGF BB and inhibited AA-induced migration. Inhibition of calcium 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 play an essential role in suppressing PDGF AA-induced migration in +/+ MMCs. During kidney development, PDGFR -mediated ROS generation and calcium influx suppress PDGF AA-induced chemotaxis in metanephric mesenchyme.
