SARM1 promotes the neuroinflammation and demyelination through IGFBP2/NF-kappa B pathway in experimental autoimmune encephalomyelitis mice

doi:10.1111/apha.13974

科研成果详情

题名	SARM1 promotes the neuroinflammation and demyelination through IGFBP2/NF-kappa B pathway in experimental autoimmune encephalomyelitis mice
作者	Zhang, Jingjing 1,2; Jin, Lingting2; Hua, Xin1,3; Wang, Mianxian2; Wang, Jiaojiao2; Xu, Xingxing2; Liu, Huitao 3; Qiu, Haoyu 2; Sun, Huankun2; Dong, Tianyingying 2; Yang, Danlu2; Zhang, Xu3; Wang, Ying 4; Huang, Zhihui1,2
发表日期	2023-06
发表期刊	ACTA PHYSIOLOGICA 影响因子和分区
语种	英语
原始文献类型	Article
关键词	EAE IGFBP2 neuroinflammation neurons SARM1
其他关键词	PROGRESSIVE MULTIPLE-SCLEROSIS ; NEURAL REGENERATION ; MODEL ; DEGENERATION ; ACTIVATION ; INJURY ; NEURODEGENERATION ; RESPONSES ; PROTECTS
摘要	AimMultiple sclerosis (MS) is an autoimmune disease, and its typical characteristics are neuroinflammation and the demyelination of neurons in the central nervous system (CNS). Sterile alpha and TIR motif containing 1 (SARM1) is an essential factor mediating axonal degeneration and SARM1 deletion reduces the neuroinflammation in spinal cord injury. This study aimed to explore the roles of SARM1 and its underlying mechanisms in MS. MethodsExperimental autoimmune encephalomyelitis (EAE, a model of MS) model was established. Immunostaining, western blot, electron microscope, and HE staining were used to examine the pathological manifestations such as inflammation, demyelination, and neuronal death in SARM1(f/f) EAE mice and SARM1(Nestin)-CKO EAE mice. In addition, RNA-seq, real-time PCR and double-immunostaining were used to examine the underlying mechanism of SARM1 in EAE mice. ResultsSARM1 was upregulated in neurons of the spinal cords of EAE mice. SARM1 knockout in CNS ameliorated EAE with less neuroinflammation, demyelination, and dead neurons. Mechanically, SARM1 knockout resulted in the reduction of insulin-like growth factor (IGF)-binding protein 2 (IGFBP2) in neurons of EAE mice, which might inhibit the neuroinflammation through inhibiting NF-kappa B signaling. Finally, activation of NF-kappa B partially aggravated the neuroinflammation and demyelination deficits of SARM1(Nestin)-CKO EAE mice. ConclusionsThese results identified the unknown role of SARM1 in the promotion of neuroinflammation and demyelination and revealed a novel drug target pathway of SARM1/IGFBP2/NF-kappa B for MS.
资助项目	National Natural Science Foundation[81971142,81971172];Natural Science Foundation of Zhejiang Province[LR21H090001,LZ23C090001];
出版者	WILEY
ISSN	1748-1708
EISSN	1748-1716
卷号	238 期号:2
DOI	10.1111/apha.13974
页数	15
WOS类目	Physiology
WOS研究方向	Physiology
WOS记录号	WOS:000975798900001
收录类别	SCIE ; PUBMED ; SCOPUS
在线发表日期	2023-04
URL	查看原文
PubMed ID	37186158
SCOPUSEID	2-s2.0-85153594868
通讯作者地址	[Huang, Zhihui]College of Pharmacy,Hangzhou Normal University,Zhejiang,Hangzhou,311121,China ; [Zhang, Xu]Department of Neurology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China ; [Wang, Ying]Clinical Research Center,Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,Zhejiang,Hangzhou,310003,China
Scopus学科分类	Physiology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/180113
专题	基础医学院（机能实验教学中心）第一临床医学院（信息与工程学院）、附属第一医院_内科学_神经内科
通讯作者	Zhang, Xu; Wang, Ying; Huang, Zhihui
作者单位	1.College of Pharmacy,Hangzhou Normal University,Zhejiang,China; 2.School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,China; 3.Department of Neurology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,China; 4.Clinical Research Center,Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,Zhejiang,China
第一作者单位	基础医学院（机能实验教学中心）
通讯作者单位	第一临床医学院（信息与工程学院）、附属第一医院_内科学_神经内科
推荐引用方式 GB/T 7714	Zhang, Jingjing,Jin, Lingting,Hua, Xin,et al. SARM1 promotes the neuroinflammation and demyelination through IGFBP2/NF-kappa B pathway in experimental autoimmune encephalomyelitis mice[J]. ACTA PHYSIOLOGICA,2023,238(2).
APA	Zhang, Jingjing., Jin, Lingting., Hua, Xin., Wang, Mianxian., Wang, Jiaojiao., ... & Huang, Zhihui. (2023). SARM1 promotes the neuroinflammation and demyelination through IGFBP2/NF-kappa B pathway in experimental autoimmune encephalomyelitis mice. ACTA PHYSIOLOGICA, 238(2).
MLA	Zhang, Jingjing,et al."SARM1 promotes the neuroinflammation and demyelination through IGFBP2/NF-kappa B pathway in experimental autoimmune encephalomyelitis mice".ACTA PHYSIOLOGICA 238.2(2023).