Role of EMT in Cardiac Fibrosis

EMT 在心脏纤维化中的作用

• 批准号: 7190546
• 负责人: ELISABETH M ZEISBERG
• 金额: $ 5.05万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-27 至 2007-06-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7190546
• 关键词: cell differentiation; endocardium; endomyocardial fibrosis; epithelium; fibroblasts; gene expression; genetically modified animals; heart cell; heart contraction; heart disorder; laboratory mouse; mesenchyme; pathologic process; postdoctoral investigator; tissue /cell culture; vascular endothelium

DESCRIPTION (provided by applicant): Cardiac fibrosis is the underlying cause for the so-called diastolic dysfunction. Cardiac fibrosis is a process of "scarring" that results in increased stiffness of the cardiac tissue. Thus, relaxation (diastole) of the heart is disturbed, and the filling of the heart impaired. Until now, specific treatment to target the progression of cardiac fibrosis is not yet available. Fibrosis is considered to follow similar pathways in distinct tissues such as the heart, kidney, lung, skin or liver. Recent studies in the kidney demonstrated that "epithelial-mesenchymal- transition" (EMT) plays an important role in the progression of fibrosis. EMT is defined as a process in which epithelial cells differentiate into activated fibroblasts. As the endocardial cushion, which consists of mesenchymal cells, evolves via EMT from cells from the endocardium during heart development (regulated by BMPs), we hypothesized that endocardial cells could transdifferentiate into fibroblasts and contribute to cardiac fibrosis. It is one aim of this proposal to study cardiac fibrosis in mice with genetically tagged endothelial cells, in which evidence could be provided that endothelial-mesenchymal-transition exists in the heart. A second aim is to investigate EMT of endothelial cells and its regulation in vitro.

描述（由申请人提供）：心脏纤维化是所谓舒张功能障碍的根本原因。心脏纤维化是导致心脏组织硬度增加的“瘢痕形成”过程。因此，心脏的放松（舒张）受到干扰，心脏的充盈受损。到目前为止，针对心脏纤维化进展的特异性治疗尚不可用。纤维化被认为在不同的组织如心脏、肾脏、肺、皮肤或肝脏中遵循相似的途径。最近的研究表明，在肾脏中的“上皮间质转化”（EMT）在纤维化的进展中起着重要作用。EMT被定义为上皮细胞分化为活化的成纤维细胞的过程。由于由间充质细胞组成的内皮细胞垫在心脏发育过程中通过EMT从内皮细胞中进化而来（受BMP调节），我们假设内皮细胞可以转分化为成纤维细胞并促进心脏纤维化。本研究的目的之一是用基因标记的内皮细胞研究小鼠的心脏纤维化，其中可以提供心脏中存在内皮-间充质转化的证据。第二个目的是研究内皮细胞的EMT及其调控。