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Effects of extracellular matrix on changes of phenotype and gene expression in vascular smooth muscle cells

细胞外基质对血管平滑肌细胞表型及基因表达变化的影响

基本信息

批准号：
04670371
负责人：
MURANO Shunichi
金额：
$ 1.09万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670371/
关键词：
Basculr smooth muscle cell Endothelial denudation Smooth muscle cell phenotype Atherosclerosi PDGF Tumor necrosis factor Extra cellular matrix バルーンカテーテル PDGFβ-レセプター大動脈中膜平滑筋細胞大動脈内膜剥離 differential screening

项目摘要

We have examined effects of endothelial denudatio of phenotype cange of vasclar smooth muscle cells(SMC). Outgrowth rate of SMC from explants of aorta 2 or 5 days after denudation was much higher than that from untreated aorta. Scavenger pathway for acetylated low density lipoprotein and autocrine secretion of growth stimulator(s) were also observed inSMC from the aorta 5 days after denudation but not in SMC from untreated aorta. These acquired pathological ahcracters were similar to those of intimal SMC from atherosclerotic lesions. These results suggest that critical point of the phenotype change is at very early time after the treatment and it occurs within the aortic media before formation of neo-intima. another experimants revealed that SMCfrom aorta of diabetic rabbits expressed PDGF beta and the SMC showed rapid growthrate responded to PDGF-AB, PDGF-BB or whole serum. The other experiments showed that tumor necrosis factor-alpha stimulated SMC to change their phenotype from contractile to synthetic type. These data suggest that early response of medial SMC to intimal injury must ve very important to regulate the following steps to formation of atherosclerosis. We are now engaging in experiments to clarify changes of gene expression in the initial step of phenotype change after endothelial denudation. After that, effects of interaction between SMC and extracellular matrix on the phenotype of SMC will be further elucidated to assess possibilities to regulate the early step of phenotype change.

我们观察了内皮剥脱对血管平滑肌细胞（SMC）表型改变的影响。主动脉剥脱后第2天和第5天的平滑肌细胞生长率明显高于未剥脱的主动脉。剥脱后5天，主动脉SMC中也观察到乙酰化低密度脂蛋白的清除途径和生长刺激剂的自分泌，但未处理主动脉SMC中未观察到。这些获得性的病理改变与动脉粥样硬化病变的内膜SMC相似。这些结果表明，表型变化的临界点是在治疗后的非常早的时间，并且在新生内膜形成之前发生在主动脉中膜内。另一实验显示，糖尿病兔主动脉平滑肌细胞表达PDGF β，对PDGF-AB、PDGF-BB或全血清均呈快速生长反应。其他实验表明，肿瘤坏死因子-α刺激SMC由收缩型向合成型转变。提示中膜SMC对内膜损伤的早期反应对动脉粥样硬化的形成起着重要的调节作用。我们正在进行实验，以阐明内皮剥脱后表型变化的初始阶段基因表达的变化。在此之后，SMC和细胞外基质之间的相互作用对SMC表型的影响将进一步阐明，以评估调节表型变化的早期步骤的可能性。