Transcription Factor Forkhead Box P (Foxp) 1 Reduces Brain Damage During Cerebral Ischemia-Reperfusion Injury in Mice Through FUN14 Domain-containing Protein 1

作者全名："Li, Yang; Changhong, Yang; Liyu, Yang; Changchang, Meng; Zeng, Linggao; Yue, Li; Jing, Zhao"

作者地址："[Li, Yang; Changchang, Meng; Jing, Zhao] Chongqing Med Univ, Sch Basic Med Sci, Dept Pathol, Chongqing 400016, Peoples R China; [Li, Yang] Chongqing Med Univ, Chongqing Key Lab Maternal & Fetal Med, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Li, Yang] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet, Chongqing 400016, Peoples R China; [Changhong, Yang] Chongqing Med Univ, Coll Basic Med, Dept Bioinformat, Chongqing, Peoples R China; [Liyu, Yang] Chongqing Med Univ, Dept Pathol, Chongqing 400016, Peoples R China; [Yue, Li] Chongqing Med Univ, Mol Med & Canc Res Ctr, Chongqing 400016, Peoples R China; [Changchang, Meng; Jing, Zhao] Chongqing Med Univ, Inst Neurosci, Chongqing 400016, Peoples R China; [Zeng, Linggao] Chongqing Inst Food & Drug Control, Chongqing 401121, Peoples R China; [Zeng, Linggao] NMPA Key Lab Qual Monitoring Narcot Drugs & Psycho, Chongqing 401121, Peoples R China; [Jing, Zhao] Chongqing Med Univ, Inst Neurosci, Dept Pathophysiol, Yixueyuan Rd 1, Chongqing 400016, Peoples R China"

通信作者："Jing, Z (通讯作者)，Chongqing Med Univ, Inst Neurosci, Dept Pathophysiol, Yixueyuan Rd 1, Chongqing 400016, Peoples R China."

来源：NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001077619500001

JCR分区：Q2

影响因子：2.9

年份：2023

卷号：530

期号：　

开始页：1

结束页：16

文献类型：Article

关键词：forkhead box P 1; cerebral ischemia/reperfusion; nod-like receptor protein 3 inflammasome; FUN14 domain-containing protein 1; mitochondrial autophagy

摘要："plays a significant role in modulating the activation of pyrin domain-containing protein 3 (NLRP3) inflammasome, which is a major contributor to the inflammatory response that exacerbates cerebral ischemia-reperfusion (I/R) injury. Despite this, the transcriptional regulation mechanism that governs mitophagy remains unclear. This study sought to explore the potential mechanism of Forkhead Box P1 (Foxp1) and its impact on cerebral I/R injury. We investigated the potential neuroprotective role of Foxp1 in cerebral I/R injury by the middle cerebral artery occlusion (MCAO) mouse model. Additionally, we assessed whether FUN14 domain-containing protein 1 (FUNDC1) could rescue the protective effect of Foxp1. Our results showed that overexpression of Foxp1 prevented brain damage during cerebral I/R injury and promoted NLRP3 inflammasome activation, whereas knockdown of Foxp1 had the opposite effect. Notably, Foxp1 overexpression directly promotes FUNDC1 expression, enhanced mitophagy activation, and inhibited the inflammatory response mediated by the NLRP3 inflammasome. Furthermore, we confirmed through chromatin immunoprecipitation (ChIP) and luciferase reporter assays that FUNDC1 is a direct target gene of Foxp1 downstream. Furthermore, the knockdown of FUNDC1 reversed the increased activation of mitophagy and suppressed NLRP3 inflammasome activation induced by Foxp1 overexpression. Collectively, our findings suggest that Foxp1 inhibits NLRP3 inflammasome activation through FUNDC1 to reduce cerebral I/R injury.(c) 2023 IBRO. Published by Elsevier Ltd. All rights reserved."

基金机构："National Natural Science Foundation of China [81671158, 82071305, 81171090]; Natural Science Youth Foundation of China [30900457]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-BHX0618]"

基金资助正文："This work was supported by the National Natural Science Foundation of China [grant numbers 81671158, 82071305, and 81171090] , the Natural Science Youth Foundation of China [grant number 30900457] , and the Natural Science Foundation of Chongqing [project approval number: CSTB2022NSCQ-BHX0618] ."