ANGIOTENSIN-II INDUCES C-FOS EXPRESSION IN SMOOTH-MUSCLE VIA TRANSCRIPTIONAL CONTROL
ANGIOTENSIN-II INDUCES C-FOS EXPRESSION IN SMOOTH-MUSCLE VIA TRANSCRIPTIONAL CONTROL
复制标题
DOI：
10.1161/01.hyp.13.6.706
复制
发表时间：
1989-06-01
期刊：
影响因子：
8.3
通讯作者：
DZAU, VJ
中科院分区：
文献类型：
--
作者：
NAFTILAN, AJ;PRATT, RE;DZAU, VJ
血管紧张素II（Ang II）已被证明会导致培养的静止大鼠主动脉平滑肌细胞肥大。这一观察结果沿着最近血管壁中血管紧张素原信使RNA（mRNA）的证实，使我们推测血管紧张素II在高血压平滑肌肥大中的作用。许多细胞对促生长剂的最早反应之一是诱导原癌基因c-fos。为了研究血管紧张素II的作用机制，我们研究了血管紧张素II对大鼠主动脉平滑肌细胞c-fos基因表达的影响，所述大鼠主动脉平滑肌细胞通过在限定的无血清培养基中生长48小时而静止。Ang Ⅱ（10（-6）-10（-10）M）可引起c-fos mRNA表达的剂量依赖性增加。这种诱导是血管紧张素受体特异性的，因为它被竞争性抑制剂saralasin完全消除。蛋白质合成的抑制并没有阻止c-fos mRNA表达的上升，它导致了c-fos mRNA的超诱导和稳定。使用核径流转录测定，我们证明，血管紧张素II刺激c-fos基因的转录速率。这种c-fos基因表达的激活可能是血管紧张素诱导平滑肌肥大的重要机制。
Angiotensin II (Ang II) has been shown to cause hypertrophy of cultured quiescent rat aortic smooth muscle cells. This observation along with the recent demonstration of angiotensinogen messenger RNA (mRNA) in the vessel wall has led us to postulate a role for Ang II in hypertensive smooth muscle hypertrophy. One of the earliest responses in a wide variety of cells in response to a growth-promoting agent is the induction of the proto-oncogene c-fos. To investigate the mechanism of the action of Ang II, we investigated the effect of Ang II on the expression of the c-fos gene in rat aortic smooth muscle cells that were made quiescent by being grown in a defined serum-free media for 48 hours. Ang II (10(-6)-10(-10) M) resulted in a dose-dependent increase in c-fos mRNA expression. This induction was angiotensin-receptor specific since it was completely abolished by the competitive inhibitor saralasin. Inhibition of protein synthesis did not block the rise in c-fos mRNA expression; it resulted in a superinduction and stabilization of the c-fos mRNA. Using a nuclear runoff transcription assay, we demonstrated that Ang II stimulated the transcription rate of the c-fos gene. This activation of c-fos gene expression may be an important mechanism in the angiotensin-induced smooth muscle hypertrophy.