Milk Exosomes from Gestational Diabetes Mellitus (GDM) and Healthy Parturient Exhibit Differential miRNAs Profiles and Distinct Regulatory Bioactivity on Hepatocyte Proliferation

微泡 外体 小RNA 妊娠期糖尿病 肝细胞 生物 细胞生物学 PI3K/AKT/mTOR通路 下调和上调 癌症研究 内分泌学 内科学 医学 信号转导 怀孕 基因 妊娠期 体外 遗传学
作者
Zhongdaixi Zheng,Jiaqi Mo,Fengjuan Lin,Li Wang,Junbin Chen,Huiyu Luo,Yuguo Liu,Chuhong Su,Xiangfu Gu,Fei Xiong,Longying Zha
出处
期刊:Molecular Nutrition & Food Research [Wiley]
卷期号:67 (16) 被引量:5
标识
DOI:10.1002/mnfr.202300005
摘要

Scope Exosomes, a novel type of bioactive component in human milk (HM), affect infant development, growth, and health. Recent studies indicate that HM exosomes and miRNAs relate to gestational diabetes mellitus (GDM). However, the miRNAs profiles and functionalities of HM exosomes from GDM parturient remain unclear. This study aims to compare the differential miRNAs in HM exosomes from GDM and healthy parturient, and investigate the HM exosomes bioactivities in regulating hepatocyte proliferation and insulin sensitivity. Methods and Results This study extracted HM exosomes from GDM (GDM‐EXO) and healthy (NOR‐EXO) parturient by ultracentrifugation, high‐throughput sequenced and compared the exosomal miRNAs profiles, and explored the regulatory bioactivities on hepatocyte proliferation in HepG2 cells and Balb/c mice. As compared to NOR‐EXO, GDM‐EXO has similar morphology, size, concentration, and exosome‐specific markers (CD9 and TSG101) expression. GDM‐EXO and NOR‐EXO specifically harbor 1299 and 8 miRNAs, respectively. Moreover, GDM‐EXO had 176 upregulated and 47 downregulated miRNAs compared with NOR‐EXO. Both GDM‐EXO and NOR‐EXO were absorbed in cultured HepG2 hepatocytes and mice liver. GDM‐EXO inhibited hepatocytes proliferation by downregulating mammalian target of rapamycin (mTOR) possibly via exosomal miR‐101‐3p delivery. Conclusion HM exosomes from GDM and healthy parturient exhibit differential miRNAs profiles and distinct regulatory bioactivity on hepatocyte proliferation.
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