MOLECULAR AND CELLULAR BIOLOGY OF CARDIAC INTERSTITIUM

心脏间质的分子和细胞生物学

• 批准号: 3362204
• 负责人: Mahboubeh Eghbali-Webb
• 金额: $ 14.46万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3362204
• 关键词: collagen; collagenase; connective tissue metabolism; extracellular matrix; gene expression; genetic regulation; genetic transcription; heart cell; in situ hybridization; laboratory rabbit; messenger RNA; nuclear runoff assay; posttranscriptional RNA processing; posttranslational modifications; protein degradation; tissue /cell culture; transforming growth factors; ventricular hypertrophy

The myocardium consists of three compartments: muscle, vasculature; and interstitium. Resorption and remodeling as part of collagen turnover, involves an initial degradation of fibrillar collagen by tissue collagenases. Accumulation of collagen in normal or pathological states can result from either enhanced collagen synthesis or inhibited collagenolytic mechanism. During natural growth and in various disease states associated with hypertrophic growth of the myocardium an impressive structural remodeling of the cardiac interstitium is evident. To date little is known about the contribution of collagenase to the remodeling of the cardiac interstitium in the normal and hypertrophied myocardium. The overall objective of this project is to study collagenase gene expression in the myocardium and to link collagenase gene regulation to the remodeling of the collagen matrix in the heart. Toward this end we will examine: collagenase gene expression in the normal myocardium and collagenase gene regulation at transcriptional level by nuclear run-on assay; post-transcriptional level by measurement of steady state levels of mRNA; and post-translational level by measurement of enzyme activity in left ventricular pressure overload hypertrophy. We will also examine the regulatory effects of transforming growth factor-beta on collagenase gene expression in cardiac cell culture.

心肌由三个隔室组成：肌肉、脉管系统;以及 interstitium. 吸收和重塑作为胶原蛋白周转的一部分， 包括纤维状胶原蛋白的初始降解， 胶原酶 正常或病理状态下胶原蛋白的积聚 可能是由于胶原蛋白合成增强或抑制 胶原溶解机制 在自然生长和各种疾病中 与心肌肥厚性生长相关的状态， 心肌的结构重塑是明显的。 到目前为止，关于胶原酶对胶原蛋白的作用知之甚少。 正常和肥厚心肌的心肌重塑 心肌 本项目的总体目标是研究 胶原酶基因在心肌中的表达与胶原酶的连接 基因调控对心脏胶原基质重塑的作用。 为此，我们将研究：胶原酶基因表达在 正常心肌与胶原酶基因转录调控 水平通过核连续测定;转录后水平通过测量 mRNA的稳态水平;和翻译后水平， 左心室压力超负荷时酶活性的测定 肥厚 我们还将研究转型的监管效果 生长因子β对心肌细胞胶原酶基因表达的影响 文化