妊娠期糖尿病（GDM）和健康产妇的牛奶外泌体表现出不同的 miRNA 谱，并对肝细胞增殖具有不同的调节生物活性。
Milk Exosomes from Gestational Diabetes Mellitus (GDM) and Healthy Parturient Exhibit Differential miRNAs Profiles and Distinct Regulatory Bioactivity on Hepatocyte Proliferation.
机构信息
Department of Nutrition and Food Hygiene, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China.
Department of Environmental Health, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China.
出版信息
Mol Nutr Food Res. 2023 Aug;67(16):e2300005. doi: 10.1002/mnfr.202300005. Epub 2023 Jun 25.
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.
范围
外泌体是母乳（HM）中一种新型生物活性成分，影响婴儿的发育、生长和健康。最近的研究表明，HM 外泌体和 miRNA 与妊娠期糖尿病（GDM）有关。然而，来自 GDM 产妇的 HM 外泌体的 miRNA 谱和功能仍不清楚。本研究旨在比较 GDM 和健康产妇 HM 外泌体中的差异 miRNA，并研究 HM 外泌体在调节肝细胞增殖和胰岛素敏感性方面的生物活性。
方法和结果
本研究通过超速离心从 GDM（GDM-EXO）和健康（NOR-EXO）产妇中提取 HM 外泌体，进行高通量测序，并比较外泌体 miRNA 谱，探索其对 HepG2 细胞和 Balb/c 小鼠肝细胞增殖的调节生物活性。与 NOR-EXO 相比，GDM-EXO 具有相似的形态、大小、浓度和外泌体特异性标志物（CD9 和 TSG101）表达。GDM-EXO 和 NOR-EXO 分别特异性携带 1299 和 8 个 miRNA。此外，与 NOR-EXO 相比，GDM-EXO 有 176 个上调和 47 个下调的 miRNA。GDM-EXO 和 NOR-EXO 均被吸收到培养的 HepG2 肝细胞和小鼠肝脏中。GDM-EXO 通过下调哺乳动物雷帕霉素靶蛋白（mTOR）可能通过外泌体 miR-101-3p 传递来抑制肝细胞增殖。
结论
来自 GDM 和健康产妇的 HM 外泌体表现出不同的 miRNA 谱，并对肝细胞增殖具有不同的调节生物活性。
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