中国科学院上海营养与健康研究所荆清等研究人员合作发现，适配蛋白Src同源2结构域含量E（SH2E）缺失导致斑马鱼心脏缺陷。相关论文于2024年9月23日在线发表在《中国药理学报》杂志上。

研究人员调查了Src同源2结构域含量E（SH2E）在心脏发育中的功能和机制。研究人员首先分析了SH2E的时空表达，然后利用CRISPR-Cas9系统构建了SH2E缺失的斑马鱼品系。研究表明，同源突变体在受精后3天（dpf）至死亡期间发展为进行性心包水肿（PCE）、心房扩张、异常的房室循环和增厚的房室壁；可诱导的SH2E过表达能够部分拯救PCE表型。

通过转录组测序分析，研究人员证明了MAPK/ERK和NF-κB信号通路可能参与SH2E缺失引起的PCE。这项研究强调了SH2E在心脏发育中的关键作用，并可能有助于识别创新的诊断技术和治疗策略以应对先天性心脏病。

据了解，适配蛋白在多种信号通路的信号转导中发挥着关键作用。Src同源2结构域含量E（SH2E）是一种在斑马鱼胚胎发育期间在血管内皮细胞和心肌中高度表达的适配蛋白。

附：英文原文

Title: Adaptor protein Src-homology 2 domain containing E (SH2E) deficiency induces heart defect in zebrafish

Author: Liang, Yu-lai, Hu, Yang-xi, Li, Fang-fang, You, Hong-min, Chen, Jian, Liang, Chun, Guo, Zhi-fu, Jing, Qing

Issue&Volume: 2024-09-23

Abstract: Adaptor proteins play crucial roles in signal transduction across diverse signaling pathways. Src-homology 2 domain-containing E (SH2E) is the adaptor protein highly expressed in vascular endothelial cells and myocardium during zebrafish embryogenesis. In this study we investigated the function and mechanisms of SH2E in cardiogenesis. We first analyzed the spatiotemporal expression of SH2E and then constructed zebrafish lines with SH2E deficiency using the CRISPR-Cas9 system. We showed that homozygous mutants developed progressive pericardial edema (PCE), dilated atrium, abnormal atrioventricular looping and thickened atrioventricular wall from 3 days post fertilization (dpf) until death; inducible overexpression of SH2E was able to partially rescue the PCE phenotype. Using transcriptome sequencing analysis, we demonstrated that the MAPK/ERK and NF-κB signaling pathways might be involved in SH2E-deficiency-caused PCE. This study underscores the pivotal role of SH2E in cardiogenesis, and might help to identify innovative diagnostic techniques and therapeutic strategies for congenital heart disease.

DOI: 10.1038/s41401-024-01392-8

Source: https://www.nature.com/articles/s41401-024-01392-8