胎盘来源的外泌体 miR-135a-5p 通过 SIRT1 激活 PI3K/AKT 信号通路促进妊娠期糖尿病发病机制。

Placenta-derived exosomal miR-135a-5p promotes gestational diabetes mellitus pathogenesis by activating PI3K/AKT signalling pathway via SIRT1.

机构信息

Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.

出版信息

J Cell Mol Med. 2023 Dec;27(23):3729-3743. doi: 10.1111/jcmm.17941. Epub 2023 Sep 4.

Abstract

Most people are aware of gestational diabetes mellitus (GDM), a dangerous pregnancy complication in which pregnant women who have never been diagnosed with diabetes develop chronic hyperglycaemia. Exosomal microRNA (miRNA) dysregulation has been shown to be a key player in the pathophysiology of GDM. In this study, we looked into how placental exosomes and their miRNAs may contribute to GDM. When compared to exosomes from healthy pregnant women, it was discovered that miR-135a-5p was elevated in placenta-derived exosomes that were isolated from the maternal peripheral plasma of GDM women. Additionally, we discovered that miR-135a-5p encouraged HTR-8/SVneo cell growth, invasion and migration. Further research revealed that miR-135a-5p activates HTR-8/SVneo cells' proliferation, invasion and migration by promoting PI3K/AKT pathway activity via Sirtuin 1 (SIRT1). The transfer of exosomal miR-135a-5p generated from the placenta could be viewed as a promising agent for targeting genes and pertinent pathways involved in GDM, according to our findings.

摘要

大多数人都知道妊娠期糖尿病(GDM),这是一种危险的妊娠并发症,一些从未被诊断患有糖尿病的孕妇会出现慢性高血糖。外泌体 microRNA(miRNA)的失调已被证明是 GDM 病理生理学中的关键因素。在这项研究中,我们研究了胎盘外泌体及其 miRNA 如何可能导致 GDM。与来自健康孕妇的外泌体相比,我们发现 GDM 孕妇外周血母源血浆分离的胎盘来源外泌体中 miR-135a-5p 升高。此外,我们发现 miR-135a-5p 促进 HTR-8/SVneo 细胞的生长、侵袭和迁移。进一步的研究表明,miR-135a-5p 通过 Sirtuin 1(SIRT1)促进 PI3K/AKT 通路的活性来促进 HTR-8/SVneo 细胞的增殖、侵袭和迁移。根据我们的研究结果,胎盘来源的外泌体 miR-135a-5p 的转移可以被视为针对 GDM 相关基因和相关途径的有前途的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1221/10718144/105270c057b3/JCMM-27-3729-g003.jpg

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