Different Functions of the Platelet-Derived Growth Factor-α and -β Receptors for the Migration and Proliferation of Cultured Baboon Smooth Muscle Cells

Migration of medial smooth muscle cells (SMCs) and their proliferation in the intima contribute to thickening of injured and atherosclerotic vessels. These events have been proposed to be regulated in part by platelet-derived growth factor (PDGF). Two separate PDGF receptors have been identified, PDGF-Rα and PDGF-Rβ. To study the functions of PDGF-Rα and PDGF-Rβ in vascular SMCs, neutralizing monoclonal antibodies (mAbs) specific for each of the two receptors were used. These antibodies allowed us to evaluate the role of each receptor for PDGF-induced proliferation and migration of cultured baboon SMCs. Both PDGF-AA and PDGF-BB stimulated SMC growth, with PDGF-BB being more potent than PDGF-AA. Studies with anti-PDGF-Rα and anti-PDGF-Rβ mAbs revealed that both PDGF receptors promoted the stimulatory signals for proliferation. In contrast, PDGF-BB stimulated SMC migration, whereas PDGF-AA had no stimulatory activity on its own. Additionally, PDGF-AA was able to suppress migration induced by PDGF-BB or fibronectin in modified Boyden's chamber assay. When PDGF-BB-induced migration was separated into chemotactic and chemokinetic activities, only the chemotactic component was inhibited by PDGF-AA. The suppression of SMC migration by PDGF-AA was eliminated by anti-PDGF-Rα mAb. In addition, PDGF-BB, in the presence of anti-PDGF-Rβ, bound only to PDGF-Rα and caused suppression of SMC migration induced by fibronectin. These results suggest that when activated by ligand binding, both PDGF-Rα and PDGF-Rβ stimulate proliferation. In contrast, only activation of PDGF-Rβ stimulates migration, whereas ligand binding to PDGF-Rα leads to inhibition of cell migration. These observations provide support for the conclusion that PDGF-Rα and PDGF-Rβ may play different roles in SMC function and may be involved in different regulatory mechanisms during vascular remodeling.