Effects of spinal cord injury associated exosomes delivered tRF-41 on the progression of spinal cord injury progression

IF 3.4 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics Pub Date : 2024-06-11 DOI:10.1016/j.ygeno.2024.110885

Hongfei Cai, Yan Zhang, Fanyu Meng, Yang Li

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引用次数: 0

Abstract

Background

Spinal cord injury (SCI) is a devastating neurological and pathological condition. Exosomal tsRNAs have reported to be promising biomarkers for cancer diagnosis and therapy. This study aimed to investigate the roles of SCI-associated exosomes, and related tsRNA mechanisms in SCI.

Methods

The serum of healthy controls and SCI patients at the acute stage were collected for exosomes isolation, and the two different exosomes were used to treat human astrocytes (HA). The cell viability, apoptosis, and cycle were determined, and the expression of the related proteins were detected by western blot. Then, the two different exosomes were sent for tsRNA sequencing, and four significant known differentially expressed tsRNAs (DE-tsRNAs) were selected for RT-qPCR validation. Finally, tRT-41 was chosen to further explore its roles and related mechanisms in SCI.

Results

After sequencing, 21 DE-tsRNAs were identified, which were significantly enriched in pathways of Apelin, AMPK, Hippo, MAPK, Ras, calcium, PI3K-Akt, and Rap1. RT-qPCR showed that tRF-41 had higher levels in the SCI-associated exosomes. Compared with the control HA, healthy exosomes did not significantly affect the growth of HA cells, but SCI-associated exosomes inhibited viability of HA cells, while promoted their apoptosis and increased the HA cells in G2/M phase; but tRF-41 inhibitor reversed the actions of SCI-associated exosomes. Additionally, SCI-associated exosomes, similar with tRF-41 mimics, down-regulated IGF-1, NGF, Wnt3a, and β-catenin, while up-regulated IL-1β and IL-6; but tRF-41 inhibitor had the opposite actions, and reversed the effects induced by SCI-associated exosomes.

Conclusions

SCI-associated exosomes delivered tRF-41 may inhibit the growth of HA through regulating Wnt/ β-catenin pathway and inflammation response, thereby facilitating the progression of SCI.

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脊髓损伤相关外泌体递送 tRF-41 对脊髓损伤进展的影响

背景：脊髓损伤（SCI）是一种破坏性的神经和病理状况。据报道，外泌体 tsRNAs 是一种很有前景的癌症诊断和治疗生物标记物。本研究旨在探讨 SCI 相关外泌体的作用以及相关 tsRNA 在 SCI 中的作用机制：方法：收集健康对照组和急性期 SCI 患者的血清进行外泌体分离，用两种不同的外泌体处理人星形胶质细胞（HA）。测定细胞活力、凋亡和周期，并通过 Western 印迹检测相关蛋白的表达。然后，将两种不同的外泌体送去进行 tsRNA 测序，并选择了四个重要的已知差异表达 tsRNA（DE-tsRNAs）进行 RT-qPCR 验证。最后，选择了 tRT-41 进一步探讨其在 SCI 中的作用和相关机制：结果：经过测序，共鉴定出21个DE-tsRNAs，它们在Apelin、AMPK、Hippo、MAPK、Ras、钙、PI3K-Akt和Rap1等通路中明显富集。RT-qPCR显示，tRF-41在SCI相关外泌体中含量较高。与对照组HA相比，健康外泌体对HA细胞的生长无明显影响，但SCI相关外泌体抑制了HA细胞的活力，同时促进了细胞凋亡，并增加了处于G2/M期的HA细胞；但tRF-41抑制剂逆转了SCI相关外泌体的作用。此外，SCI相关外泌体与tRF-41模拟物相似，可下调IGF-1、NGF、Wnt3a和β-catenin，同时上调IL-1β和IL-6；但tRF-41抑制剂的作用相反，可逆转SCI相关外泌体诱导的效应：结论：SCI相关外泌体释放的tRF-41可通过调节Wnt/ β-catenin通路和炎症反应抑制HA的生长，从而促进SCI的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genomics 生物-生物工程与应用微生物

CiteScore

9.60

自引率

2.30%

发文量

260

审稿时长

60 days

期刊介绍： Genomics is a forum for describing the development of genome-scale technologies and their application to all areas of biological investigation. As a journal that has evolved with the field that carries its name, Genomics focuses on the development and application of cutting-edge methods, addressing fundamental questions with potential interest to a wide audience. Our aim is to publish the highest quality research and to provide authors with rapid, fair and accurate review and publication of manuscripts falling within our scope.