Both Platelet-Derived Growth Factor Receptor (PDGFR)-α and PDGFR-β Promote Murine Fibroblast Cell Migration

Abstract

Cell motility plays a critical role for many physiological and pathological processes including wound healing, fibrosis, angiogenesis, and tumor metastasis. Platelet-derived growth factor (PDGF) is among the most potent stimuli for mesenchymal cell migration. The PDGF B-chain homodimer PDGF BB activates both α- and β-receptor subunits (α-PDGFR and β-PDGFR), and promotes cell migration in many cell types including fibroblasts and smooth muscle cells. PDGF-A chain homodimer PDGF AA activates α-PDGFR only, and its role for cell migration is still debatable. PDGF BB, but not PDGF AA, induces smooth muscle cell migration. Interestingly, α-PDGFR was shown to antagonize β-PDGFR-induced smooth muscle cell migration. In the present study, we investigated the role of α-PDGFR and β-PDGFR in PDGF-mediated cell migration of murine fibroblasts (NIH 3T3). Unlike smooth muscle cells, both PDGF AA and PDGF BB promoted NIH 3T3 cell migration. The effect of PDGF BB activation of β-PDGFR alone for cell migration was examined using previously established NIH 3T3 clones in which α-PDGFR signaling is inhibited by a dominant-negative α-PDGFR, or an antisense construct of α-PDGFR. PDGF BB activation of β-PDGFR alone was sufficient to induce cell migration, but the efficiency was significantly lower compared to PDGF activation of both receptors. These results showed that both α- and β-PDGFRs promote fibroblast cell migration and their effects are additive. Taken together, we propose that cell-type specific α-PDGFR signaling is critical for regulation of mesenchymal cell migration in response to PDGF isoform, whereas β-PDGFR mainly promotes cell migration.