Activated TREM1-mediated MAPK signaling in endothelial cells caused by highly expressed STAT1 is associated with intracranial aneurysms occurrence and rupture.

IF 3.5 2区生物学 Q3 CELL BIOLOGY

Molecular and Cellular Biochemistry Pub Date : 2024-12-11 DOI:10.1007/s11010-024-05173-z

Hao Zhu, Ge Gao, Yingang Wu, Yang Wang, Yu Chen, Chaoshi Niu

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引用次数: 0

Abstract

Intracranial aneurysm (IA) poses significant health risks, yet the specific mRNA profiles and regulatory mechanisms distinguishing unruptured IA (UIA) from ruptured IA (RIA) remain unclear. This study aimed to elucidate these differences through comprehensive mRNA analysis. We employed RNA sequencing to compare mRNA expression patterns among control individuals, UIA patients, and RIA patients. Differential expression analysis identified triggering receptor expressed on myeloid cells 1 (TREM1) as a potential biomarker for IA occurrence and rupture, which was validated in an expanded cohort. In vitro experiments revealed that TREM1 overexpression in human umbilical vein endothelial cells (HUVECs) inhibited proliferation, angiogenesis, and migration while promoting apoptosis and inflammation. Bioinformatic predictions and subsequent chromatin immunoprecipitation assays confirmed signal transducer and activator of transcription 1 (STAT1) as a transcriptional regulator of TREM1. STAT1 overexpression in HUVECs activated the MAPK signaling pathway and mimicked the effects of TREM1 overexpression, which were reversible by TREM1 inhibition. Conversely, P38 MAPK inhibition produced opposite effects, which were negated by STAT1 overexpression. This study identifies TREM1 as a potential biomarker for IA occurrence and rupture, likely regulated by STAT1, offering new avenues for non-invasive IA intervention strategies.

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STAT1高表达导致内皮细胞中trem1介导的MAPK信号激活与颅内动脉瘤的发生和破裂有关。

颅内动脉瘤（IA）具有显著的健康风险，但区分未破裂IA （UIA）和破裂IA （RIA）的特定mRNA谱和调控机制尚不清楚。本研究旨在通过全面的mRNA分析来阐明这些差异。我们采用RNA测序来比较对照个体、UIA患者和RIA患者的mRNA表达模式。差异表达分析发现髓样细胞上表达的触发受体1 （TREM1）是IA发生和破裂的潜在生物标志物，并在扩大的队列中得到验证。体外实验表明，TREM1在人脐静脉内皮细胞（HUVECs）中的过表达抑制了细胞增殖、血管生成和迁移，同时促进了细胞凋亡和炎症。生物信息学预测和随后的染色质免疫沉淀试验证实了转录1的信号换能器和激活器（STAT1）是TREM1的转录调节因子。STAT1在HUVECs中的过表达激活了MAPK信号通路，并模拟了TREM1过表达的影响，这是通过抑制TREM1可逆的。相反，抑制P38 MAPK产生相反的效果，这被STAT1过表达否定。本研究确定TREM1是IA发生和破裂的潜在生物标志物，可能受STAT1调控，为无创IA干预策略提供了新的途径。

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

Molecular and Cellular Biochemistry 生物-细胞生物学

CiteScore

8.30

自引率

2.30%

发文量

293

审稿时长

1.7 months

期刊介绍： Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.