Maternal exosomes in diabetes contribute to the cardiac development deficiency

Maternal exosomes in diabetes contribute to the cardiac development deficiency
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糖尿病中的母体外泌体导致心脏发育缺陷

DOI:
10.1016/j.bbrc.2016.12.097
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发表时间:
2017
影响因子:
3.1
通讯作者:
Yuan L
Yuan L
中科院分区:
生物学4区
文献类型:
--
作者:
Shi R;Zhao L;Cai W;Wei M;Zhou X;Yang G;Yuan L

文献摘要

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母体糖尿病可增加先天性心脏病(CHD)的风险,但确切机制尚未完全阐明。本研究通过在交配前注射链脲佐菌素诱导糖尿病妊娠C57 BL/6小鼠。RNA-seq分析显示,与正常对照小鼠相比,糖尿病妊娠小鼠血液中外泌体miRNA含量发生了显著变化。发现这些miRNAs中的多个参与心脏发育调节。此外,荧光标记的外泌体和金纳米颗粒可以在胚胎发育期间穿过胎盘屏障并渗透到胚胎器官/组织,包括心脏。注射糖尿病母体外泌体显著增加了正常受体妊娠小鼠患CHD的风险。综上所述,我们可以得出结论,糖尿病母体外泌体可能通过miRNAs穿过母胎屏障并导致心脏发育缺陷,为CHD的预防和治疗提供了新的见解。
Maternal diabetes mellitus induces an increased risk of congenital heart defects (CHD), however, the exact mechanisms are still not fully illustrated. In this study, diabetic pregnant C57BL/6 mice were induced by injection of streptozotocin before mating. Compared with the control normal mice, diabetic pregnant mice displayed significant changes of the exosomal miRNA contents in the blood, as revealed by RNA-seq analysis. Multiple of these miRNAs were found involved in cardiac development regulation. Moreover, fluorescence labeled exosomes and gold nanoparticles could cross the placenta barrier and infiltrated into the embryonic organs/tissues, including the heart, during embryonic development. Injection of diabetic maternal exosomes strikingly increased the risk of CHD in the normal recipient pregnant mice. Taken together, we could draw the conclusion that maternal exosomes in diabetes could cross the maternal-fetal barrier and contribute to the cardiac development deficiency possibly via miRNAs, providing new insights in CHD prevention and treatment.