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Am J Physiol Renal Physiol 282: F211-F219, 2002. First published August 8, 2001; doi:10.1152/ajprenal.0323.2000
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Vol. 282, Issue 2, F211-F219, February 2002

Effect of platelet-derived growth factor isoforms in rat metanephric mesenchymal cells

Jill M. Ricono1,2, Mazen Arar3, Goutam Ghosh Choudhury4,5, and Hanna E. Abboud1,2,5

Departments of 1 Medicine and 3 Pediatrics, and 2 Institute of Biotechnology, Department of Molecular Medicine, 4 The University of Texas Health Science Center and Geriatric Research, Education and Clinical Center, 5 South Texas Veterans Health Care System, San Antonio, Texas 78229-3900

Platelet-derived growth factor (PDGF) B-chain or PDGF beta -receptor-deficient mice lack mesangial cells. To explore potential mechanisms for failure of PDGF A-chain to rescue mesangial cell phenotype, we investigated the biological effects and signaling pathways of PDGF AA and PDGF BB in metanephric mesenchymal (MM) cells isolated from rat kidney. PDGF AA caused modest cell migration but had no effect on DNA synthesis, unlike PDGF BB, which potently stimulated migration and DNA synthesis. PDGF AA and PDGF BB significantly increased the activities of phosphatidylinositol 3-kinase (PI 3-K) and mitogen-activated protein kinase (MAPK). PDGF BB was more potent than PDGF AA in activating PI 3-K or MAPK in these cells. Pretreatment of MM cells with the MAPK kinase (MEK) inhibitor PD-098059 abrogated PDGF BB-induced DNA synthesis, whereas the PI 3-K inhibitor wortmannin had a very modest inhibitory effect on DNA synthesis (approximately Delta 20%). On the other hand, wortmannin completely blocked PDGF AA- and PDGF BB-induced migration, whereas PD-098059 had a modest inhibitory effect on cell migration. These data demonstrate that activation of MAPK is necessary for the mitogenic effect of PDGF BB, whereas PI 3-K is required for the chemotactic effect of PDGF AA and PDGF BB. Although PDGF AA stimulates PI 3-K and MAPK activity, it is not mitogenic and only modestly chemotactic. Collectively, the data may have implications related to the failure of PDGF AA to rescue mesangial cell phenotype in PDGF B-chain or PDGF-beta -receptor deficiency.

kidney; development; mesangial cell; signal transduction


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