Early Growth Response Gene-1 Deficiency Interrupts TGFβ1 Signaling Activation and Aggravates Neurodegeneration in Experimental Autoimmune Encephalomyelitis Mice  

作　　者：Yunyi Lan Xinyan Han Fei Huang Hailian Shi Hui Wu Liu Yang Zhibi Hu Xiaojun Wu 

机构地区：[1]Shanghai Key Laboratory of Compound Chinese Medicines,The Ministry of Education Key Laboratory for Standardization of Chinese Medicines,The State Administration of TCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine,Institute of Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China [2]Central Laboratory,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,200021,China

出　　处：《Neuroscience Bulletin》2024年第3期283-292,共10页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82074043,82104425,82374065,and 81673626);the China Postdoctoral Science Foundation(2021M702217).

摘　　要：Early growth response protein 1(Egr-1)triggers the transcription of many genes involved in cell growth,differentiation,synaptic plasticity,and neurogenesis.However,its mechanism in neuronal survival and degeneration is still poorly understood.This study demonstrated that Egr-1 was down-regulated at mRNA and protein levels in the central nervous system(CNS)of experimental autoimmune encephalomyelitis(EAE)mice.Egr-1 knockout exacerbated EAE progression in mice,as shown by increased disease severity and incidence;it also aggravated neuronal apoptosis,which was associated with weakened activation of the BDNF/TGFβ1/MAPK/Akt signaling pathways in the CNS of EAE mice.Consistently,Egr-1 siRNA promoted apoptosis but mitigated the activation of BDNF/TGFβ1/MAPK/Akt signaling in SH-SY5Y cells.Our results revealed that Egr-1 is a crucial regulator of neuronal survival in EAE by regulating TGFβ1-mediated signaling activation,implicating the important role of Egr-1 in the pathogenesis of multiple sclerosis as a potential novel therapy target.

关 键 词：Early growth response protein 1 Transforming growth factor-beta 1 Multiple sclerosis Experimental autoimmune encephalomyelitis NEURODEGENERATION 

分 类 号：R741[医药卫生—神经病学与精神病学]