血管紧张素Ⅱ对血管平滑肌血小板源生长因子受体β亚单位的调节

Role of angiotensin Ⅱ in the regulation of platelet-derived growth factor receptor β subunit of vascular smooth muscle

目的 :观察血管紧张素Ⅱ对血管平滑肌血小板源生长因子 (PDGF)受体 β亚单位的调节 ,探讨两条信号转导途径的交互作用在血管平滑肌细胞 (VSMC)增殖中的意义。方法 :制备两肾一夹肾性高血压大鼠模型 ,免疫印迹法检测主动脉组织PDGF受体 β亚单位的含量。培养大鼠主动脉VSMC ,观察血管紧张素Ⅱ (AngⅡ )对PDGF受体 β亚单位的影响。 结果 :两肾一夹大鼠术后 8周动脉血压明显增高 ,同时主动脉PDGF受体 β亚单位的表达高于对照组 12 6 6 % (P <0 0 5 )。AngⅡ刺激培养的VSMC可导致PDGF受体 β亚单位上调 192 74% (P <0 0 1) ,该效应可被Ⅰ型AngⅡ受体 (AT1)的拮抗剂losartan和磷脂酶C(phospholipasec ,PLC)的抑制剂U7312 2完全阻断 (P <0 0 1) ,但仅被丝裂原活化蛋白激酶激酶抑制剂PD980 5 9部分阻断 (P <0 0 1)。结论 :AngⅡ可以通过AT1及下游的信号分子PLC上调PDGF受体 β亚单位的表达 。

AIM: To investigate the crosstalk between angiotensin Ⅱ (AngⅡ)-mediated and platelet-derived growth factor (PDGF)-mediated signal transduction in vascular smooth muscle proliferation.METHODS: A model of renal hypertension was made by two kidney/one-clip operation. Level of PDGF receptor β subunit of aorta was measured by Western Blot analysis. The effect of Ang Ⅱ on PDGF receptor β subunit expression was investigated in culture rat aortic vascular smooth muscle cells (VSMC).RESULTS: Systolic blood pressure obviously increased at 8th week after operation, whereas the level of PDGF receptor β subunit of aorta significantly increased by 126.6% ( P<0.05 ) in 2K1C rats compared with control group. The expression of PDGF receptor β subunit in cultured VSMC stimulated by AngⅡ was higher than that of control by 192.74%( P<0.01 ). The effect of AngⅡ was inhibited remarkably by pretreated with losartan, a kind of specific AngⅡ receptor 1 (AT 1) subtype antagonist and U73122, a kind of phospholipase C inhibitor. The effect was partly blocked by PD98059, which inhibit the activity of mitogen-activated, ERK-activating kinase (MEK).CONCLUSION: AngⅡ-induced PDGF receptor β subunit expression is regulated by the AT 1 and its downstream signal molecule-PLC and ERK, might participate in the intracellular signal transduction pathway. [