TREM‐1 Promotes Microglial Pyroptosis and Mitochondrial Fission in Intracerebral Hemorrhage via the PI3K/AKT Pathway

上睑下垂 神经炎症 线粒体分裂 小胶质细胞 细胞生物学 基因敲除 化学 信号转导 神经科学 药理学 星形胶质细胞 医学 神经保护 线粒体 程序性细胞死亡 神经退行性变 脑出血 基因剔除小鼠 泛连接蛋白 少突胶质细胞
作者
Yuan An,Tingting Zhai,Fang Wang,Kaiyuan Zhang,Mengzhao Feng,Dengpan Song,Zhihua Li,Fuyou Guo
出处
期刊:The FASEB Journal [Wiley]
卷期号:39 (19): e71115-e71115 被引量:1
标识
DOI:10.1096/fj.202501909r
摘要

TREM-1, a pro-inflammatory factor, aggravates neuroinflammation following intracerebral hemorrhage (ICH). Both pyroptosis and mitochondrial dysfunction play a vital role in the further injury of ICH. However, whether TREM-1 regulates microglial pyroptosis and mitochondrial fission, and the potential mechanisms underlying these processes, remains unclear. A mouse model of ICH was established via stereotactic injection of collagenase VII-S. To knock down TREM-1 in vivo, AAV9-Iba1-TREM-1 was injected into the right basal ganglia. Additionally, the TREM-1-specific inhibitor LP17 was administered intranasally. Neurological function was assessed using behavioral assessments. In vitro, BV2 was stimulated with hemin to mimic ICH. LP17, NLRP3 inhibitor MCC950, TREM-1 agonist antibody Mab1187, and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 were used to investigate the mechanisms underlying TREM-1-mediated microglial pyroptosis and mitochondrial fission. Immunofluorescence staining, Western blot, RT-qPCR, and transmission electron microscopy were employed to evaluate microglial pyroptosis and mitochondrial fission. Both pharmacological inhibition and AAV-mediated knockdown of TREM-1 significantly improved neurological function, attenuated microglial pyroptosis and mitochondrial fission in ICH mice. TREM-1 was shown to drive microglial pyroptosis through the NLRP3 inflammasome. Furthermore, the PI3K/AKT signaling pathway was demonstrated to regulate TREM-1-induced microglial pyroptosis and mitochondrial fission. This study provides the first evidence that TREM-1 promotes microglial pyroptosis and mitochondrial fission following ICH via the PI3K/AKT signaling pathway. These findings highlight TREM-1 as a potential therapeutic target for mitigating neuroinflammation and neuronal damage in ICH.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
郭WL发布了新的文献求助20
1秒前
星辰大海应助heisa采纳,获得10
1秒前
1秒前
2秒前
Hello应助洋1采纳,获得10
2秒前
LLL发布了新的文献求助10
2秒前
完美世界应助711notfound采纳,获得10
2秒前
Lay发布了新的文献求助10
2秒前
2秒前
小海绵发布了新的文献求助10
2秒前
3秒前
3秒前
星辰大海应助小乐采纳,获得10
3秒前
起名废人应助zzzz采纳,获得10
3秒前
圆圆滚滚发布了新的文献求助10
3秒前
搜集达人应助yyyyy采纳,获得30
4秒前
赘婿应助CH采纳,获得10
5秒前
5秒前
justonce发布了新的文献求助10
6秒前
6秒前
7秒前
7秒前
7秒前
7秒前
7秒前
12发布了新的文献求助10
7秒前
CodeCraft应助cqz采纳,获得10
8秒前
脑洞疼应助彩色迎丝采纳,获得30
8秒前
双峰山发布了新的文献求助10
8秒前
yyyjjj发布了新的文献求助10
8秒前
meixinmeifei发布了新的文献求助10
8秒前
wqa1472发布了新的文献求助10
8秒前
8秒前
从容紫寒发布了新的文献求助10
8秒前
洋1发布了新的文献求助10
9秒前
9秒前
11秒前
11秒前
bkagyin应助科研阿白采纳,获得10
11秒前
时简发布了新的文献求助10
11秒前
高分求助中
Principles of Economics, 11th Edition 10000
University Physics with Modern Physics, 16th edition 10000
(应助此贴封号)【重要!!请各用户(尤其是新用户)详细阅读】【科研通的精品贴汇总】 10000
48V Low-voltage Power Distribution Network (PDN) Architecture Industry Report, 2024 800
ズームレンズの光学設計に関する研究 800
Fundamentals of Pharmaceutical and Biologics Regulations: A Global Perspective, Second Edition 700
Matrix Methods in Data Mining and Pattern Recognition Second Edition 610
热门求助领域 (近24小时)
化学 材料科学 医学 生物 纳米技术 工程类 有机化学 化学工程 生物化学 计算机科学 内科学 物理 复合材料 催化作用 细胞生物学 无机化学 光电子学 物理化学 电极 基因
热门帖子
关注 科研通微信公众号,转发送积分 7294839
求助须知:如何正确求助?哪些是违规求助? 8913385
关于积分的说明 18872341
捐赠科研通 6961264
什么是DOI,文献DOI怎么找? 3210127
关于科研通互助平台的介绍 2379484
邀请新用户注册赠送积分活动 2186400