Autophagy is involved in high glucose-induced heart tube malformation

Wang, Guang; Huang, Wen; Cui, Shu Dan; Li, Shuai; Wang, Xiao yu; Li, Yan; Chuai, Manli; Cao, Liu; Li, Jiangchao; Lu, Daxiang; Yang, Xuesong

doi:10.1080/15384101.2014.1000170

Cited by 31 publications

(24 citation statements)

References 54 publications

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“…Cell trace with DiI (Carbocyanine dye 1,1V‐dioctadecyl‐3,3,3V,3V‐tetramethyl indocarbocyanine perchlorate, Molecular Probes, Inc.) was performed according to a standard protocol as described previously by Wang et al ().…”

Section: Methodsmentioning

confidence: 99%

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

Gao¹,

Wang²,

Zhang³

et al. 2018

Journal Cellular Physiology

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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.

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Section: Methodsmentioning

confidence: 99%

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

Gao¹,

Wang²,

Zhang³

et al. 2018

Journal Cellular Physiology

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“…High-salinity culture [1.125% NaCl:albumen (1:1); calculated final osmolality of the culture, 300 mosm l −1 ] was applied to one side of stage HH3 onwards chick embryos during early chicken (EC) culture as previously described (He et al, 2013(He et al, , 2014Wang et al, 2015a). The other side of embryos treated with simple saline served as the control [0.7% NaCl: albumen (1:1); calculated final osmolality of the culture, 300 mosm l ).…”

Section: Blood Island Formation In Chick Embryosmentioning

confidence: 99%

“…The housekeeping gene PPIA ( peptidylprolyl isomerase A) was run in parallel to confirm that equal amounts of RNA were used in each reaction. The ratio between intensity of the fluorescently stained bands corresponding to genes and PPIA was calculated to quantify the level of the transcripts for those mRNAs (De Simone et al, 2005;Wang et al, 2015a). The RT-PCR result was representative of four independent experiments.…”

Section: Rna Isolation and Rt-pcrmentioning

confidence: 99%

The impact of high salt exposure on cardiovascular development in the early chick embryo

Wang

Zhang

Wei

et al. 2015

Journal of Experimental Biology

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In this study, we show that high-salt exposure dramatically increases chick mortality during embryo development. As embryonic mortality at early stages mainly results from defects in cardiovascular development, we focused on heart formation and angiogenesis. We found that high-salt exposure enhanced the risk of abnormal heart tube looping and blood congestion in the heart chamber. In the presence of high salt, both ventricular cell proliferation and apoptosis increased. The high osmolarity induced by high salt in the ventricular cardiomyocytes resulted in incomplete differentiation, which might be due to reduced expression of Nkx2.5 and GATA4. Blood vessel density and diameter were suppressed by exposure to high salt in both the yolk sac membrane (YSM) and chorioallantoic membrane models. In addition, high-salt-induced suppression of angiogenesis occurred even at the vasculogenesis stage, as blood island formation was also inhibited by high-salt exposure. At the same time, cell proliferation was repressed and cell apoptosis was enhanced by high-salt exposure in YSM tissue. Moreover, the reduction in expression of HIF2 and FGF2 genes might cause high-saltsuppressed angiogenesis. Interestingly, we show that high-salt exposure causes excess generation of reactive oxygen species (ROS) in the heart and YSM tissues, which could be partially rescued through the addition of antioxidants. In total, our study suggests that excess generation of ROS might play an important role in high-saltinduced defects in heart and angiogenesis.

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“…12 One of the other ways to promote autophagy is by inducing ER stress such as Tunicamycin, which is a glycosylation inhibitor. Another frequently-used pharmacological compound in autophagy study is 3-MA, 13,14 which blocks the formation of LC3-II and p62 degradation, so that it could inhibit ATG5-induced autophagy.…”

Section: Introductionmentioning

confidence: 99%

Proper autophagy is indispensable for angiogenesis during chick embryo development

Shi

Lai³

et al. 2016

Cell Cycle

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People have known that autophagy plays a very important role in many physiological and pathological events. But the role of autophagy on embryonic angiogenesis still remains obscure. In this study, we demonstrated that Atg7, Atg8 and Beclin1 were expressed in the plexus vessels of angiogenesis at chick yolk sac membrane and chorioallantoic membrane. Interfering in autophagy with autophagy inducer or inhibitor could restrict the angiogenesis in vivo, which might be driven by the disorder of angiogenesisrelated gene expressions, and also lead to embryonic hemorrhage, which was due to imperfection cell junctions in endothelial cells including abnormal expressions of tight junction, adheren junction and desmosome genes. Using HUVECs, we revealed that cell viability and migration ability changed with the alteration of cell autophagy exposed to RAPA or 3-MA. Interestingly, tube formation assay showed that HUVECs ability of tube formation altered with the change of Atg5, Atg7 and Atg8 manipulated by the transfection of their corresponding siRNA or plasmids. Moreover, the lost cell polarity labeled by F-actin and the absenced b-catenin in RAPA-treated and 3-MA-treated cell membrane implied intracellular cytoskeleton alteration was induced by the activation and depression of autophagy. Taken together, our current experimental data reveal that autophagy is really involved in regulating angiogenesis during embryo development.

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Autophagy is involved in high glucose-induced heart tube malformation

Cited by 31 publications

References 54 publications

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

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

The impact of high salt exposure on cardiovascular development in the early chick embryo

Proper autophagy is indispensable for angiogenesis during chick embryo development

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