Cofilin Phosphorylation Mediates Proliferation in Response to Platelet-Derived Growth Factor-BB in Rat Aortic Smooth Muscle Cells

• Published in: Journal of Pharmacological Sciences 2008, Vol.108(3), pp.372-379
• Main Authors: Won, Kyung-Jong, Park, Seung Hwa, Park, Taekyu, Lee, Chang-Kwon, Lee, Hwan Myung, Choi, Wahn Soo, Kim, Sun-Jong, Park, Pyo-Jam, Jang, Hyung-Kwan, Kim, Soon Heum, Kim, Bokyung
• Format: Article
• Language: English
• Subjects: Animals; Aorta - metabolism; Becaplermin; c-Jun N-terminal kinase (JNK); Cell Proliferation - drug effects; Cells, Cultured; cofilin; Cofilin 2 - genetics; Cofilin 2 - metabolism; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Intracellular Signaling Peptides and Proteins - metabolism; Male; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - enzymology; Myocytes, Smooth Muscle - metabolism; Phosphoprotein Phosphatases - antagonists & inhibitors; Phosphoprotein Phosphatases - metabolism; Phosphorylation; Platelet-Derived Growth Factor - metabolism; platelet-derived growth factor-BB (PDGF-BB); proliferation; Protein Kinase Inhibitors - pharmacology; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins c-sis; rat aortic smooth muscle cell (RASMC); Rats; Rats, Sprague-Dawley; RNA Interference; RNA, Small Interfering - metabolism; src-Family Kinases - antagonists & inhibitors; src-Family Kinases - metabolism; Syk Kinase; Time Factors
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.FP0072354

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.