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ErbB 信号在心脏发育和疾病中的作用。

ErbB signaling in cardiac development and disease.

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721-0207, USA.

出版信息

Semin Cell Dev Biol. 2010 Dec;21(9):929-35. doi: 10.1016/j.semcdb.2010.09.011. Epub 2010 Oct 7.

Abstract

The ErbB family of receptor tyrosine kinases (RTKs) is a family of receptors that allow cells to interact with the extracellular environment and transduce signals to the nucleus that promote differentiation, migration and proliferation necessary for proper heart morphogenesis and function. This review focuses on the role of the ErbB family of receptor tyrosine kinases, and their importance in proper heart morphogenesis, as well as their role in maintenance and function of the adult heart. Studies from transgenic mouse models have shown the importance of ErbB receptors in heart development, and provide insight into potential future therapeutic targets to help reduce congenital heart defect (CHD) mortality rates and prevent disease in adults. Cancer therapeutics have also shed light to the ErbB receptors and signaling network, as undesired side effects have demonstrated their importance in adult cardiomyocytes and prevention of cardiomyopathies. This review will discuss ErbB receptor tyrosine kinases (RTK) in heart development and disease including valve formation and partitioning of a four-chambered heart as well as cardiotoxicity when ErbB signaling is attenuated in adults.

摘要

表皮生长因子受体家族(ErbB family)属于受体酪氨酸激酶(receptor tyrosine kinases,RTKs),是一类能够使细胞与细胞外环境相互作用,并将信号转导至细胞核的受体,从而促进适当的心脏形态发生和功能所必需的分化、迁移和增殖。本综述重点介绍了表皮生长因子受体家族的受体酪氨酸激酶的作用及其在适当的心脏形态发生中的重要性,以及它们在成年心脏的维持和功能中的作用。来自转基因小鼠模型的研究表明,ErbB 受体在心脏发育中具有重要作用,并为潜在的未来治疗靶点提供了深入了解,有助于降低先天性心脏病(CHD)死亡率并预防成年人的疾病。癌症治疗也为 ErbB 受体及其信号网络提供了启示,因为意想不到的副作用表明它们在成年心肌细胞中的重要性以及预防心肌病。本综述将讨论 ErbB 受体酪氨酸激酶(RTK)在心脏发育和疾病中的作用,包括瓣膜形成和四腔心脏的分隔,以及 ErbB 信号减弱时的心脏毒性。

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