Cofilin phosphorylation mediates proliferation in response to platelet-derived growth factor-BB in rat aortic smooth muscle cells.

Cofilin, an actin-binding protein, is essential for a variety of cell responses. In this study, we investigated the correlation between proliferation and cofilin phosphorylation in response to platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells (RASMCs). The phosphorylation of cofilin and activity of mitogen-activated protein kinase (MAPK) were measured by Western analyses and proliferation in RASMCs was measured by BrdU incorporation assays. The phosphorylation of cofilin in RASMCs was decreased by PDGF-BB treatment at 10 min, but recovered to the level of the quiescent state at 60 min. PDGF-BB-induced dephosphorylation of cofilin was inhibited by pretreatment with piceatannol (a spleen tyrosine kinase [Syk] inhibitor), PP2 (a Src inhibitor), or SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor), but not by PD98059, an inhibitor of extracellular signal-regulated kinase 1/2. PDGF-BB increased JNK activity and proliferation, and these responses were suppressed by kinase inhibitors and small interference RNA-cofilin. The results suggest that PDGF-BB-induced dephosphorylation of cofilin can be promoted via the JNK pathway, which is regulated by both Syk and Src kinases and that cofilin dephosphorylation may be involved in PDGF-BB-induced RASMC proliferation.