Autophagy is involved in high glucose-induced heart tube malformation
Autophagy is involved in high glucose-induced heart tube malformation
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DOI：
10.1080/15384101.2014.1000170
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发表时间：
2015-03
期刊：
影响因子：
4.3
通讯作者：
Guang Wang;Wen-qing Huang;Shu-dan Cui;Shuai Li;Xiao-yu Wang;Yan Li;Manli Chuai;Liu Cao;Jiangchao Li;Da-xiang Lu;Xuesong Yang
中科院分区：
文献类型：
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作者：
Guang Wang;Wen-qing Huang;Shu-dan Cui;Shuai Li;Xiao-yu Wang;Yan Li;Manli Chuai;Liu Cao;Jiangchao Li;Da-xiang Lu;Xuesong Yang
妊娠前和妊娠期糖尿病对心脏发育都有不良影响，但对心管形成早期的影响知之甚少。利用早期原肠胚，我们研究了高糖对心管形成过程的影响，特别是在初级心场阶段。我们证明，高糖暴露导致3种类型的心管畸形：1）心室肥大，2）心室肥大伴心绞痛和3）心室肥大伴心绞痛伴双侧主心管融合异常。其次，我们发现这些畸形的心管表型可能主要源于原肠胚形成的心前中胚层细胞的迁移异常，而不是细胞增殖的发育过程中的双边初级心野原基。自噬诱导剂雷帕霉素（RAPA）的治疗导致与高糖相似的心管畸形表型。此外，高糖暴露促进了早期鸡组织中关键自噬蛋白LC3B的表达。Atg7在双侧主心管融合部位有强表达。这些结果提示自噬可能参与了高糖诱导的心管畸形的发生过程。
Both pre-gestational and gestational diabetes have an adverse impact on heart development, but little is known about the influence on the early stage of heart tube formation. Using early gastrulating chick embryos, we investigated the influence of high glucose on the process of heart tube formation, specifically during the primary heart field phase. We demonstrated that high-glucose exposure resulted in 3 types of heart tube malformation: 1) ventricular hypertrophy, 2) ventricular hypertrophy with dextrocardia and 3) ventricular hypertrophy and dextrocardia with the fusion anomaly of a bilateral primary heart tube. Next, we found that these malformation phenotypes of heart tubes might mainly originate from the migratory anomaly of gastrulating precardiac mesoderm cells rather than cell proliferation in the developmental process of bilateral primary heart field primordia. The treatment of rapamycin (RAPA), an autophagy inducer, led to a similar heart tube malformation phenotype as high glucose. Additionally, high-glucose exposure promoted the expression of the key autophagy protein LC3B in early chick tissue. Atg7 is strongly expressed in the fusion site of bilateral primary heart tubes. All of these data imply that autophagy could be involved in the process of high-glucose-induced malformation of the heart tube.