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

Jill M. Ricono, Mazen Y Arar, Goutam Ghosh-choudhury, Hanna E. Abboud

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Platelet-derived growth factor (PDGF) B-chain or PDGF β-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 Δ20%). 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-β-receptor deficiency.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume282
Issue number2 51-2
StatePublished - 2002

Fingerprint

Platelet-Derived Growth Factor
Phosphatidylinositol 3-Kinase
Protein Isoforms
Mitogen-Activated Protein Kinases
Mesangial Cells
Proto-Oncogene Proteins c-sis
Platelet-Derived Growth Factor Receptors
DNA
Mitogen-Activated Protein Kinase Kinases
Cell Movement
Phenotype
platelet-derived growth factor BB
Kidney

Keywords

  • Development
  • Kidney
  • Mesangial cell
  • Signal transduction

ASJC Scopus subject areas

  • Physiology

Cite this

Effect of platelet-derived growth factor isoforms in rat metanephric mesenchymal cells. / Ricono, Jill M.; Arar, Mazen Y; Ghosh-choudhury, Goutam; Abboud, Hanna E.

In: American Journal of Physiology - Renal Physiology, Vol. 282, No. 2 51-2, 2002.

Research output: Contribution to journalArticle

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