Essential roles of Meltrin β (ADAM19) in heart development
Essential roles of Meltrin β (ADAM19) in heart development
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DOI：
10.1016/j.ydbio.2003.10.021
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发表时间：
2004-03-01
影响因子：
2.7
通讯作者：
Sehara-Fujisawa, A
中科院分区：
文献类型：
--
作者：
Kurohara, K;Komatsu, K;Sehara-Fujisawa, A
心脏的形态发生需要内膜垫组织的发育，内膜垫组织产生膜隔和瓣膜。在这里，我们表明，Meltrin β/ADAM 19，一种新的金属蛋白酶-去整合素，参与发展的endoarthritis垫。缺乏Meltrin beta的小鼠表现出室间隔缺损（VSD）和未成熟的瓣膜，并且大多数动物在出生后不久就死亡。在内膜垫的发育过程中，内膜上皮细胞的上皮-间充质转化（EMT）产生了大部分构成隔膜和瓣膜主要成分的垫间充质。Meltrin β在心内膜垫的上皮细胞和间充质中表达。在没有Meltrinbeta的情况下，垫在隔膜形成区域中小或薄，并且显示心脏胶状成分的重塑较差;这两个特征都表明内膜垫的生长和分化受损。当胚胎成纤维细胞稀疏培养时，Meltrin β缺乏的细胞表现出I型Neuregulin（在内皮细胞中表达的ErbB配体之一）的异常胞外域脱落。这些结果表明Meltrin β对ErbB配体的蛋白水解调节对于心脏正常发育的必要性。(C)2003年爱思唯尔公司All rights reserved.
Morphogenesis of the heart requires development of the endocardial cushion tissue that gives rise to the membranous septa and valves. Here we show that Meltrin beta/ADAM19, a novel metalloprotease-disintegrin, participates in the development of the endocardial cushion. Mice lacking Meltrin beta exhibit ventricular septal defect (VSD) and immature valves, and most of the animals die soon after birth. During development of the endocardial cushion, epithelial-mesenchymal transformation (EMT) of endocardial epithelial cells generates most of the cushion mesenchymes that constitute the main components of the septa and valves. Meltrin beta is expressed in both the epithelia and the mesenchymes of the endocardial cushion. In the absence of Meltrinbeta, the cushion is small or thin in the septum-forming region and show poor remodeling of cardiac jelly components; both of these characteristics suggest impaired growth and differentiation of the endocardial cushion. When embryonic fibroblasts are cultured sparsely, Meltrin beta-lacking cells exhibit aberrant ectodomain shedding of type I Neuregulin, one of the ErbB ligands expressed in endocardial cells. These results suggest the necessity of proteolytic regulation of ErbB ligands by Meltrin beta for proper heart development. (C) 2003 Elsevier Inc. All rights reserved.