High salt‐induced excess reactive oxygen species production resulted in heart tube malformation during gastrulation

Gao, Lin-rui, Wang, Guang, Zhang, Jing, Li, Shuai, Chuai, Manli, Bao, Yongping, Hocher, Berthold and Yang, Xuesong (2018) High salt‐induced excess reactive oxygen species production resulted in heart tube malformation during gastrulation. Journal of Cellular Physiology, 233 (9). pp. 7120-7133. ISSN 0021-9541

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Abstract

An association has been proved between high salt consumption and cardiovascular mortality. In vertebrates, the heart is the first functional organ to be formed. However, it is not clear whether high‐salt exposure has an adverse impact on cardiogenesis. Here we report high‐salt exposure inhibited basement membrane breakdown by affecting RhoA, thus disturbing the expression of Slug/E‐cadherin/N‐cadherin/Laminin and interfering with mesoderm formation during the epithelial‐mesenchymal transition(EMT). Furthermore, the DiI+ cell migration trajectory in vivo and scratch wound assays in vitro indicated that high‐salt exposure restricted cell migration of cardiac progenitors, which was caused by the weaker cytoskeleton structure and unaltered corresponding adhesion junctions at HH7. Besides, down‐regulation of GATA4/5/6, Nkx2.5, TBX5, and Mef2c and up‐regulation of Wnt3a/β‐catenin caused aberrant cardiomyocyte differentiation at HH7 and HH10. High‐salt exposure also inhibited cell proliferation and promoted apoptosis. Most importantly, our study revealed that excessive reactive oxygen species(ROS)generated by high salt disturbed the expression of cardiac‐related genes, detrimentally affecting the above process including EMT, cell migration, differentiation, cell proliferation and apoptosis, which is the major cause of malformation of heart tubes.

Item Type: Article
Uncontrolled Keywords: high salt,chick embryo,heart tube,reactive oxygen species,cardiac progenitor migration and differentiation
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 06 Feb 2018 10:30
Last Modified: 18 Mar 2020 00:54
URI: https://ueaeprints.uea.ac.uk/id/eprint/66228
DOI: 10.1002/jcp.26528

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