CircPTP4A2 Promotes Microglia Polarization in Cerebral Ischemic Stroke via miR-20b-5p/YTHDF1/TIMP2 Axis.

IF 3.3 4区医学 Q2 NEUROSCIENCES

NeuroMolecular Medicine Pub Date : 2023-12-01 Epub Date: 2023-09-14 DOI:10.1007/s12017-023-08751-4

Xianxin Kang, Yanhui Cao, Guodong Sun, Dongsheng Fei, Kai Kang, Xianglin Meng, Mingyan Zhao

{"title":"CircPTP4A2 Promotes Microglia Polarization in Cerebral Ischemic Stroke via miR-20b-5p/YTHDF1/TIMP2 Axis.","authors":"Xianxin Kang, Yanhui Cao, Guodong Sun, Dongsheng Fei, Kai Kang, Xianglin Meng, Mingyan Zhao","doi":"10.1007/s12017-023-08751-4","DOIUrl":null,"url":null,"abstract":"<p><p>Activated microglia play dual roles in ischemic stroke (IS) according to its polarization states. Herein, we investigated the function of circPTP4A2 in regulating microglia polarization in IS. IS models were established by MACO/R and OGD/R treatment. TTC staining was employed to detect cerebral infarct size. Cell vitality was measured using CCK-8 assay. CD16 and CD206 levels were examined using flow cytometry. The interactions between circPTP4A2, miR-20b-5p, and YTHDF1 were analyzed by dual-luciferase reporter gene, RIP, or RNA pull-down assays. circPTP4A2 was upregulated in IS patients. circPTP4A2 knockdown alleviated MCAO/R-induced cerebral injury in mice. circPTP4A2 knockdown promoted microglia M2 polarization after OGD/R. circPTP4A2 promoted YTHDF1 expression by sponging miR-20b-5p. The promoting effect of circPTP4A2 knockdown on microglia M2 polarization was abrogated by miR-20b-5p inhibition. YTHDF1 activated the NF-κB pathway by increasing TIMP2 mRNA stability and expression. circPTP4A2 downregulation promoted microglia M2 polarization to inhibit IS development by regulating the miR-20b-5p/YTHDF1/TIMP2/NF-κB axis.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":" ","pages":"501-515"},"PeriodicalIF":3.3000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NeuroMolecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12017-023-08751-4","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/14 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Activated microglia play dual roles in ischemic stroke (IS) according to its polarization states. Herein, we investigated the function of circPTP4A2 in regulating microglia polarization in IS. IS models were established by MACO/R and OGD/R treatment. TTC staining was employed to detect cerebral infarct size. Cell vitality was measured using CCK-8 assay. CD16 and CD206 levels were examined using flow cytometry. The interactions between circPTP4A2, miR-20b-5p, and YTHDF1 were analyzed by dual-luciferase reporter gene, RIP, or RNA pull-down assays. circPTP4A2 was upregulated in IS patients. circPTP4A2 knockdown alleviated MCAO/R-induced cerebral injury in mice. circPTP4A2 knockdown promoted microglia M2 polarization after OGD/R. circPTP4A2 promoted YTHDF1 expression by sponging miR-20b-5p. The promoting effect of circPTP4A2 knockdown on microglia M2 polarization was abrogated by miR-20b-5p inhibition. YTHDF1 activated the NF-κB pathway by increasing TIMP2 mRNA stability and expression. circPTP4A2 downregulation promoted microglia M2 polarization to inhibit IS development by regulating the miR-20b-5p/YTHDF1/TIMP2/NF-κB axis.

Abstract Image

查看原文本刊更多论文

CircPTP4A2 通过 miR-20b-5p/YTHDF1/TIMP2 轴促进缺血性脑卒中小胶质细胞极化

活化的小胶质细胞根据其极化状态在缺血性中风（IS）中扮演着双重角色。在此，我们研究了circPTP4A2在IS中调节小胶质细胞极化的功能。通过MACO/R和OGD/R处理建立了IS模型。采用TTC染色检测脑梗塞大小。用CCK-8检测法测量细胞活力。流式细胞术检测了CD16和CD206的水平。通过双荧光素酶报告基因、RIP或RNA pull-down实验分析了circPTP4A2、miR-20b-5p和YTHDF1之间的相互作用。circPTP4A2敲除可减轻MCAO/R诱导的小鼠脑损伤；circPTP4A2敲除可促进OGD/R后小胶质细胞M2极化；circPTP4A2可通过海绵状miR-20b-5p促进YTHDF1的表达。抑制miR-20b-5p可减轻circPTP4A2敲除对小胶质细胞M2极化的促进作用。通过调节miR-20b-5p/YTHDF1/TIMP2/NF-κB轴，下调circPTP4A2可促进小胶质细胞M2极化，从而抑制IS的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

NeuroMolecular Medicine 医学-神经科学

CiteScore

7.10

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： NeuroMolecular Medicine publishes cutting-edge original research articles and critical reviews on the molecular and biochemical basis of neurological disorders. Studies range from genetic analyses of human populations to animal and cell culture models of neurological disorders. Emerging findings concerning the identification of genetic aberrancies and their pathogenic mechanisms at the molecular and cellular levels will be included. Also covered are experimental analyses of molecular cascades involved in the development and adult plasticity of the nervous system, in neurological dysfunction, and in neuronal degeneration and repair. NeuroMolecular Medicine encompasses basic research in the fields of molecular genetics, signal transduction, plasticity, and cell death. The information published in NEMM will provide a window into the future of molecular medicine for the nervous system.