Early proto-oncogene expression in rat aortic smooth muscle cells following endothelial removal.
Early proto-oncogene expression in rat aortic smooth muscle cells following endothelial removal.
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发表时间：
1990-10
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通讯作者：
Joseph M. Miano;R. R. Tota-R.;Niksa;Vlasic;Kenneth J. Danishefsky;Michael B. Stemerman
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作者：
Joseph M. Miano;R. R. Tota-R.;Niksa;Vlasic;Kenneth J. Danishefsky;Michael B. Stemerman
为了研究血管平滑肌细胞在体内增殖的机制，在血管球囊去内皮化（BDE）后，采用Northern blot方法检测c-fos、c-jun和c-myc的mRNA水平。采用酶解血管壁的方法分离血管内侧平滑肌细胞（SMC）。主动脉平滑肌细胞（SMC） c-fos和c-jun mRNA水平在BDE后30分钟内同时被诱导，并在1.5小时内降至基线水平，c-myc mRNA直到血管损伤后1小时才开始升高。c-myc水平在2小时达到峰值，并持续4小时后逐渐下降。来源于酶处理的对照主动脉的平滑肌细胞，不经历BDE表达c-fos和c-jun，但没有显示c-myc信息的证据。相比之下，未经酶处理的非bde全主动脉（包括中膜和外膜）显示出明显的c-myc信号，但未能表达c-fos和c-jun。对经酶处理的主动脉外膜的相应检查表明，该组织是所有三种原癌基因的来源。本研究的结果证明了迄今为止报道的最早的血管损伤的体内分子标记，并暗示SMC原癌基因的表达与SMC增殖的起始有关。此外，这些发现提示了原癌基因诱导的两种途径，即：(1)血管壁操纵和(2)体液刺激。
To study the mechanism(s) of vascular smooth muscle cell proliferation in vivo, mRNA levels of c-fos, c-jun, and c-myc were determined by Northern blot analysis following vascular balloon de-endothelialization (BDE). Medial smooth muscle cells (SMC) were separated and studied by enzymatic digestion of the vessel wall. mRNA levels of c-fos and c-jun from aortic smooth muscle cells (SMC) were simultaneously induced within 30 minutes of BDE and declined to baseline by 1.5 hours, c-myc mRNA did not begin to increase until 1 hour after vascular injury. Levels of c-myc peaked at 2 hours and were sustained for an additional 4 hours before gradually declining. Smooth muscle cells derived from enzyme-treated control aortae that did not undergo BDE expressed c-fos and c-jun, but showed no evidence of c-myc message. In contrast, nonenzymatically treated, non-BDE whole aortae (containing both media and adventitia) demonstrated a prominent c-myc signal, but failed to express c-fos and c-jun. Corresponding examination of adventitia derived from enzyme-treated aortae showed this tissue to be a source of all three proto-oncogenes. The results of this study demonstrate the earliest in vivo molecular markers of vascular injury reported to date and implicate SMC proto-oncogene expression in the initiation of SMC proliferation. Furthermore these findings suggest two avenues for proto-oncogene induction, that are due to (1) vessel wall manipulation and (2) humoral stimulation.