TRANSFORMING GROWTH FACTOR BETA-1 IN NORMAL HEART AND IN INFARCTION

正常心脏和梗死心脏中的转化生长因子 Beta-1

• 批准号: 3920217
• 负责人: F BAZOBERRY
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3920217
• 关键词: angiogenesis; cell differentiation; cell growth regulation; fibrinolysis; laboratory rat; myocardial infarction; platelets; tissue /cell culture; transforming growth factors; wound healing

Transforming growth factor beta 1 is a polypeptide originally isolated from platelets which is a regulator of cell growth and differentiation. In vitro, given certain cultured conditions TGbeta 1 can cause fibroblasts to grow in soft Agar - a property of transformed cells. More often, though, TGF beta is an inhibitor of growth, for example it inhibits FGF stimulation of endothelial cell proliferation. However, it cooperates with FGF in induction of the embryonic mesoderm. TGF beta 1 also regulates production of extracellular matrix, and in particular regulates plasminogen activators and the PA inhibitor, PAI-1. Plasmin can activate latent TGF beta 1. All these features suggest that TGF beta 1 could play one or more important roles if present in the heart. In this study, we used a polyclonal antiserum raised by Flanders and Sporn against the first 30 residues of TGF beta 1. Specificity of the immunocyhtochemistry was indicated by the absence of staining with normal (non-immune) serum or with immune serum pre- absorbed with excise TGF beta 1. Immunohistochemical evidence of TGF beta1 was found in cardiac myocytes and in smooth muscle cells and endothelial cells of sections of normal rat hearts. Supportive evidence was the presence of a 2.4 Kb mRNA transcript on northern blotting. Coronary ligations were then performed in these rats. Between 1 and 6 hours after ligation ir TGF beta-1 began to be lost from cardiac myocytes, sparing only 1-2 layers of cells in the subendocardium and around vessels, which are presumably viable cells. Interestingly, by 6 hours these cells seemed to actually have an increase in immunoreactivity, as did myocytes in the border zone. These effects suggest that TGF beta-1 may will be involved in fibrinolysis, wound healing or angiogenesis in the setting of myocardial infarction.

转化生长因子β 1是一种多肽， 分离自血小板，其是细胞生长的调节剂， 分化 在体外，在一定的培养条件下 TGF β 1可以导致成纤维细胞在软琼脂中生长-这是一种特性 转化的细胞。 然而，更常见的是，TGF β是一种抑制剂， 例如，它抑制FGF刺激内皮细胞 细胞增殖 但是，它在诱导方面与FGF合作 胚胎中胚层。 TGF β 1也调节生产 特别是调节纤溶酶原 激活剂和PA抑制剂派-1。 纤溶酶可以激活 潜伏性TGF β 1。 所有这些特征表明，TGF β 1 如果存在于心脏中，可以发挥一个或多个重要作用。 在这项研究中，我们使用了弗兰德斯提出的多克隆抗血清 和针对TGF β 1的前30个残基的Sporn。 特异性 免疫细胞化学的结果表明， 用正常（非免疫）血清或用免疫前血清染色， 被切除的TGF β 1吸收。 免疫组织化学证据表明 在心肌细胞和平滑肌细胞中发现TGF β 1 和正常大鼠心脏切片的内皮细胞。 支持性 证据是在北方细胞上存在一个2.4 Kb的mRNA转录本。 印迹 然后在这些大鼠中进行冠状动脉结扎。 月1 和6小时后，ir TGF β-1开始从 心肌细胞，仅保留1-2层细胞， 血管下和血管周围，这可能是可行的 细胞 有趣的是，6小时后，这些细胞似乎 免疫反应性增加， 区 这些作用表明TGF β 1可能参与了 在纤维蛋白溶解、伤口愈合或血管生成中， 心肌梗死