Kim Su Jin, Kim Su Yung, Kwon Chae Hwa, Kim Yong Keun
Department of Pediatrics, College of Medicine, Pusan National University, Pusan 602-739, South Korea.
Growth Factors. 2007 Apr;25(2):77-86. doi: 10.1080/08977190701398977.
It has been known that growth factors such as fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) can promote proliferation and migration in a variety of cell types including osteoblastic cells. However, the mechanism underlying their action has not been clearly defined. The present study was undertaken to examine the effect of FGF and PDGF on cell proliferation and migration and to determine the role of extracellular signal-regulated kinase (ERK) and Akt in action of FGF and PDGF in osteoblastic cells. FGF enhanced proliferation in a dose- and time-dependent manner, whereas it did not affect cell migration. FGF induced a transient activation of ERK, but not Akt, which was inhibited by an inhibitor of MEK, the upstream kinase of ERK, but not by inhibitors of PI3K/Akt (LY294002), epidermal growth factor receptor (EGFR, AG1478), and Src (PP2). FGF-induced proliferation was inhibited by inhibitors of MEK/ERK and Src pathways. Exposure of cells to FGF stimulated transition of cell cycle from the G1 phase to S phase and increased phosphorylation of Rb. FGF-induced phosphorylation of Rb was attenuated by inhibitors of MEK/ERK and Src pathways. Cell migration studies indicated that PDGF stimulated migration, but it had no effect on cell proliferation. PDGF induced activation of ERK and Akt. The ERK activatin was inhibited by the Src inhibitor and the Akt activation was inhibited by inhibitors of EGFR and Src. PDGF-induced migration was inhibited by inhibitors of MEK/ERK, PI3K/Akt, EGFR and Src pathways. Taken together, these findings suggest that the MEK/ERK and Src pathways play an important role in the FGF-induced proliferation and signaling pathways involving MEK/ERK, EGFR, Src and PI3K/Akt mediate the PDGF-induced migration. These data are of importance in understanding the roles of these growth factors in osteoblastic cell proliferation and migration.
已知成纤维细胞生长因子（FGF）和血小板衍生生长因子（PDGF）等生长因子可促进包括成骨细胞在内的多种细胞类型的增殖和迁移。然而，其作用的潜在机制尚未明确界定。本研究旨在检测FGF和PDGF对细胞增殖和迁移的影响，并确定细胞外信号调节激酶（ERK）和Akt在FGF和PDGF作用于成骨细胞中的作用。FGF以剂量和时间依赖性方式增强增殖，而不影响细胞迁移。FGF诱导ERK的瞬时激活，但不诱导Akt的激活，这被ERK的上游激酶MEK的抑制剂所抑制，而不被PI3K/Akt（LY294002）、表皮生长因子受体（EGFR，AG1478）和Src（PP2）的抑制剂所抑制。FGF诱导的增殖被MEK/ERK和Src途径的抑制剂所抑制。细胞暴露于FGF刺激细胞周期从G1期向S期转变，并增加Rb的磷酸化。FGF诱导的Rb磷酸化被MEK/ERK和Src途径的抑制剂所减弱。细胞迁移研究表明，PDGF刺激迁移，但对细胞增殖无影响。PDGF诱导ERK和Akt的激活。ERK的激活被Src抑制剂所抑制，Akt的激活被EGFR和Src的抑制剂所抑制。PDGF诱导的迁移被MEK/ERK、PI3K/Akt、EGFR和Src途径的抑制剂所抑制。综上所述，这些发现表明MEK/ERK和Src途径在FGF诱导的增殖中起重要作用，涉及MEK/ERK、EGFR、Src和PI3K/Akt的信号通路介导PDGF诱导的迁移。这些数据对于理解这些生长因子在成骨细胞增殖和迁移中的作用具有重要意义。
