TY - JOUR
T1 - High salt-induced excess reactive oxygen species production resulted in heart tube malformation during gastrulation
AU - Gao, Lin Rui
AU - Wang, Guang
AU - Zhang, Jing
AU - Li, Shuai
AU - Chuai, Manli
AU - Bao, Yongping
AU - Hocher, Berthold
AU - Yang, Xuesong
N1 - 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.
PY - 2018/9
Y1 - 2018/9
N2 - 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.
AB - 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.
KW - cardiac progenitor migration and differentiation
KW - chick embryo
KW - heart tube
KW - high salt
KW - reactive oxygen species
U2 - 10.1002/jcp.26528
DO - 10.1002/jcp.26528
M3 - Article
C2 - 29574800
AN - SCOPUS:85047818937
SN - 0021-9541
VL - 233
SP - 7120
EP - 7133
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 9
ER -