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压力超负荷大鼠心肌中I型和III型纤维状胶原蛋白以及IV型基底膜胶原蛋白基因表达的调控

Regulation of fibrillar collagen types I and III and basement membrane type IV collagen gene expression in pressure overloaded rat myocardium.

作者信息

Chapman D, Weber K T, Eghbali M

机构信息

Cardiovascular Institute, Michael Reese Hospital, University of Chicago Pritzker School of Medicine, Ill 60616.

出版信息

Circ Res. 1990 Oct;67(4):787-94. doi: 10.1161/01.res.67.4.787.

Abstract

Left ventricular hypertrophy is based on cardiac myocyte growth. The hypertrophic process can be considered heterogeneous based on whether it also includes a remodeling and accumulation of fibrillar types I and III collagens that are responsible for impaired myocardial stiffness. In the heart, the messenger RNA (mRNA) for fibrillar collagen types I and III has been detected only in cardiac fibroblasts, whereas mRNA for basement membrane collagen type IV is present in both fibroblasts and myocytes. We studied the early and long-term expression of these collagenous proteins in rat myocardium after abdominal aortic banding with renal ischemia. Complementary DNA probes for rat pro-alpha 2 (I), mouse type III and mouse type IV collagens, and chicken beta-actin were used. Northern and dot blot analysis on total RNA extracted from left ventricular tissue indicated a sixfold increase in steady-state levels of mRNA for collagen type I on day 3 of abdominal aortic banding, which had declined to control levels by day 7 where it remained rather constant at 4 and 8 weeks. Type III collagen showed a similar pattern of gene expression after banding. mRNA levels for type IV collagen, on the other hand, were elevated on day 1 after banding, returning to control at day 7 and remaining constant. Actin mRNA levels also increased on day 1 of banding, followed by a rapid return to control levels. Monospecific antibody to types I and III collagens and immunofluorescent light microscopy on frozen sections of the myocardium revealed that at 1 week after banding, the distribution and density of these collagens were similar to those of control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

左心室肥厚基于心肌细胞生长。基于肥厚过程是否还包括负责心肌僵硬度受损的I型和III型纤维状胶原蛋白的重塑和积累,该肥厚过程可被认为是异质性的。在心脏中,仅在心脏成纤维细胞中检测到I型和III型纤维状胶原蛋白的信使核糖核酸(mRNA),而IV型基底膜胶原蛋白的mRNA则存在于成纤维细胞和心肌细胞中。我们研究了肾缺血性腹主动脉缩窄后大鼠心肌中这些胶原蛋白的早期和长期表达。使用了大鼠原α2(I)、小鼠III型和小鼠IV型胶原蛋白以及鸡β-肌动蛋白的互补DNA探针。对从左心室组织提取的总RNA进行的Northern和斑点印迹分析表明,腹主动脉缩窄第3天,I型胶原蛋白的mRNA稳态水平增加了6倍,到第7天已降至对照水平,在4周和8周时保持相当稳定。III型胶原蛋白在缩窄后表现出类似的基因表达模式。另一方面,IV型胶原蛋白的mRNA水平在缩窄后第1天升高,第7天恢复到对照水平并保持恒定。肌动蛋白mRNA水平在缩窄第1天也增加,随后迅速恢复到对照水平。针对I型和III型胶原蛋白的单特异性抗体以及对心肌冰冻切片进行的免疫荧光显微镜检查显示,缩窄后1周,这些胶原蛋白的分布和密度与对照动物相似。(摘要截短于250字)

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