The epicardium is required for sarcomeric maturation and cardiomyocyte growth in the ventricular compact layer mediated by TGFβ and FGF before the onset of coronary circulation.
The epicardium is required for sarcomeric maturation and cardiomyocyte growth in the ventricular compact layer mediated by TGFβ and FGF before the onset of coronary circulation.
复制标题
在冠脉循环开始之前，心外膜是 TGFβ 和 FGF 介导的心室致密层中肌节成熟和心肌细胞生长所必需的。
DOI：
10.1111/cga.12048
复制
发表时间：
2014
影响因子：
1.3
通讯作者：
Nakajima Y.
中科院分区：
文献类型：
--
作者：
Takahashi M;Yamagishi T;Narematsu M;Kamimura T;Kai M;Nakajima Y.
心外膜起源于心外膜器官(PE)，是发育中心脏的第三层上皮层，对心脏的形态发生至关重要。心外膜缺陷导致发育中的脑室形成较薄的致密层；然而，导致致密层发育受损的机制尚不清楚。使用鸡胚胎心脏，我们通过外科手术消融或阻断PE的迁移来产生心外膜缺陷的心脏，并研究了致密心肌变薄的机制。心外膜缺损性室壁变薄致密心肌的肌节成熟(Z线间距)和心肌细胞生长(大小)受到影响，表现为磷酸化Smad2和磷酸化ERK的数量减少以及转化生长因子β2和成纤维细胞生长因子2的表达减少。转化生长因子β和成纤维细胞生长因子是肌节成熟和心肌细胞生长所必需的。在显性阴性(DN)-ALK5(dN-转化生长因子β受体I)和dN-FGF1受体的体外转染法中，心肌变薄致密。我们的结果表明，未成熟的肌节和小的心肌细胞是导致心外膜缺乏的薄致密层的原因，转化生长因子β和成纤维细胞生长因子介导的心外膜依赖的信号在冠脉循环开始之前的心室致密层的发育中发挥了作用。
The epicardium, which is derived from the proepicardial organ (PE) as the third epithelial layer of the developing heart, is crucial for ventricular morphogenesis. An epicardial deficiency leads to a thin compact layer for the developing ventricle; however, the mechanisms leading to the impaired development of the compact layer are not well understood. Using chick embryonic hearts, we produced epicardium‐deficient hearts by surgical ablation or blockade of the migration of PE and examined the mechanisms underlying a thin compact myocardium. Sarcomeric maturation (distance between Z‐lines) and cardiomyocyte growth (size) were affected in the thin compact myocardium of epicardium‐deficient ventricles, in which the amounts of phospho‐smad2 and phospho‐ERK as well as expression of transforming growth factor (TGF)β2 and fibroblast growth factor (FGF)2 were reduced. TGFβ and FGF were required for the maturation of sarcomeres and growth of cardiomyocytes in cultured ventricles.In ovoco‐transfection of dominant negative (dN)‐Alk5 (dN‐TGFβ receptor I) and dN‐FGF receptor 1 to ventricles caused a thin compact myocardium. Our results suggest that immature sarcomeres and small cardiomyocytes are the causative architectures of an epicardium‐deficient thin compact layer and also that epicardium‐dependent signaling mediated by TGFβ and FGF plays a role in the development of the ventricular compact layer before the onset of coronary circulation.