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长链非编码 RNA-GAS5 通过调节 Th1/Th2 平衡与复发性流产的发生有关。

LncRNA-GAS5 related to the processes of recurrent pregnancy loss by regulating Th1/Th2 balance.

机构信息

Department of Reproductive Center, Huai'an Maternal and Child Health Care Hospital, Xuzhou Medical University, Huai'an, Jiangsu, China.

Department of gynaecology, Huai'an Maternal and Child Health Care Hospital, Xuzhou Medical University, Huai'an, Jiangsu, China.

出版信息

Kaohsiung J Med Sci. 2021 Jun;37(6):479-486. doi: 10.1002/kjm2.12360. Epub 2021 Jan 28.

Abstract

Recurrent pregnancy loss (RPL) is defined as three or more consecutive spontaneous loss of pregnancy and the reason of 50% RPL is unknown. GAS5 is a long non-coding RNA, which has been found to be an immune responses regulator and to be relate to autoimmune diseases. However, the roles of GAS5 during the pathophysiological processes of RPL is unclear. In the present study, the levels of GAS5 were examined in the plasma and trophoblasts from 30 patients with RPL and 15 healthy controls. GAS5 was found overexpressed in patients with RPL and positively correlated with the protein levels of TNF-α in the plasma and trophoblasts. Predicted by bioinformatics tools and confirmed by luciferase assay, GAS5 was identified to function as a competing endogenous RNA (ceRNA) binding with miR-140-5p and protects TNF-α expression in HTR-8/SVneo cells and primary trophoblasts. Activated Naïve T cells co-cultured with the medium from GAS5 overexpression HTR-8/SVneo cells or primary trophoblasts exhibited Th1 bias by expression more IFN-γ, TNF-α and less IL-4, IL-10. In conclusion, GAS5 was overexpressed in the plasma and trophoblasts from RPL patients, which contributes to Th1 bias by binding with miR-140-5p.

摘要

复发性妊娠丢失(RPL)定义为连续三次或更多次自然妊娠丢失,50%的 RPL 原因不明。GAS5 是一种长链非编码 RNA,已被发现是免疫反应调节剂,并与自身免疫性疾病有关。然而,GAS5 在 RPL 的病理生理过程中的作用尚不清楚。在本研究中,检测了 30 例 RPL 患者和 15 例健康对照者的血浆和滋养层中的 GAS5 水平。发现 RPL 患者的 GAS5 表达上调,并与血浆和滋养层中 TNF-α 的蛋白水平呈正相关。通过生物信息学工具预测并通过荧光素酶测定证实,GAS5 作为一种竞争性内源性 RNA(ceRNA)与 miR-140-5p 结合,并保护 HTR-8/SVneo 细胞和原代滋养层中 TNF-α 的表达。激活的 Naïve T 细胞与过表达 GAS5 的 HTR-8/SVneo 细胞或原代滋养层的培养基共培养后,通过表达更多的 IFN-γ、TNF-α和更少的 IL-4、IL-10 表现出 Th1 偏向。总之,RPL 患者的血浆和滋养层中 GAS5 表达上调,通过与 miR-140-5p 结合导致 Th1 偏向。

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