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

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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.

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 - Sep 2018

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Gastrulation
Congenital Heart Defects
Reactive Oxygen Species
Salts
Cell Movement
Epithelial-Mesenchymal Transition
Cell proliferation
Cadherins
Cell Proliferation
Apoptosis
Catenins
Gastropoda
Laminin
Mesoderm
Cytoskeleton
Basement Membrane
Cardiac Myocytes
Vertebrates
Cell Differentiation
Assays

Keywords

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

Cite this

Gao, Lin Rui ; Wang, Guang ; Zhang, Jing ; Li, Shuai ; Chuai, Manli ; Bao, Yongping ; Hocher, Berthold ; Yang, Xuesong. / High salt-induced excess reactive oxygen species production resulted in heart tube malformation during gastrulation. In: Journal of Cellular Physiology. 2018 ; Vol. 233, No. 9. pp. 7120-7133.
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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.",
keywords = "cardiac progenitor migration and differentiation, chick embryo, heart tube, high salt, reactive oxygen species",
author = "Gao, {Lin Rui} and Guang Wang and Jing Zhang and Shuai Li and Manli Chuai and Yongping Bao and Berthold Hocher and Xuesong Yang",
note = "NSFC, Grant numbers: 81741016, 31771331; Science and Technology Planning Project of Guangdong Province, Grant numbers: 2017A020214015, 2017A050506029; Science and Technology Program of Guangzhou, Grant number: 201710010054; Guangdong Natural Science Foundation, Grant number: 2016A030311044; Fundamental Research Funds for the Central Universities, Grant number: 21617466; Students Research Training Program Fund, Grant number: 201610559024.",
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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; Yang, Xuesong.

In: Journal of Cellular Physiology, Vol. 233, No. 9, 09.2018, p. 7120-7133.

Research output: Contribution to journalArticle

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AU - Bao, Yongping

AU - Hocher, Berthold

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