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

Lin Rui Gao, Guang Wang, Jing Zhang, Shuai Li, Manli Chuai, Yongping Bao, Berthold Hocher, Xuesong Yang

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)
    270 Downloads (Pure)

    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.

    Original languageEnglish
    Pages (from-to)7120-7133
    Number of pages14
    JournalJournal of Cellular Physiology
    Volume233
    Issue number9
    Early online date25 Mar 2018
    DOIs
    Publication statusPublished - Sept 2018

    Keywords

    • cardiac progenitor migration and differentiation
    • chick embryo
    • heart tube
    • high salt
    • reactive oxygen species

    ASJC Scopus subject areas

    • Physiology
    • Clinical Biochemistry
    • Cell Biology

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