丝裂原活化蛋白激酶参与血小板源生长因子刺激的大鼠主动脉平滑肌细胞增殖(英文)

选择大鼠主动脉平滑肌细胞作为细胞模型 ,观察丝裂原活化蛋白激酶 ( MAPK)信号通路在血小板源生长因子 ( PDGF)诱导的血管平滑肌细胞( VSMC)增殖中的作用。用 3 H]Td R参入率作为衡量 VSMC增殖的指标 ,以 Western-印迹方法 ,用磷酸化一抗测 MAPK磷酸化的程度作为衡量 MAPK活性的指标 ,实验结果发现 ,PDGF( 0 .0 2 - 2 0μg·L-1)诱导 VSMC增殖呈剂量依赖性。 PDGF( 2μg· L-1)能持续性激活 MAPK。用 PD980 59( 1 0 -1 0 0 mol· L-1)预处理 1 5min后 ,MAPK活性较对照组均有明显差别 ( P<0 .0 5) .MAPK反义寡核苷酸能明显抑制 PDGF诱导的 MAPK的激活 ,并明显抑制 VSMC3 H]Td R参入。上述结果表明 ,MAPK参与 PDGF促细胞增殖的信号途经 ,它的持续性激活与细胞增殖有关 ,针对 p42 /p44MAPK设计的反义寡核苷酸类能有效抑制 PDGF诱导的血管平滑肌细胞增殖。

Mitogen-activated protein kinase mediated platelet-derived growth factor- induced rat vascular smooth muscle cell proliferation

The role of p42/p44 mitogen-activated protein kinase (MAPK) on platelet- derived growth factor (PDGF) induced rat vascular smooth muscle cell (VSMC) proliferation was observed. The results showed that PDGF increased ［³H］thymidine incorporation in concentration dependent manner. Maximal activation of p42/p44 MAPK by PDGF occurred at 15 min and persisted for 12 h. PD98059, a synthetic inhibitor of MAPK kinase (MAPKK), inhibited PDGF-induced phosphorylation of MAPK and DNA synthesis. Treatment with 0.2 μmol·L^-1 MAPK antisense oligode-oxynucleotides for 48 h reduced phosphorylated p42/p44 MAPK protein expression and inhibited VSMC ［³H］thymidine incorporation stimulated by PDGF. The results suggest that sustained p42/p44 MAPK activity be essential to PDGF-induced rat VSMC proliferation. The inhibition of this signaling protein may be a useful approach for preventing vascular intimal hyperplasia.