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早期生长反应基因-1 缺失中断 TGFβ1 信号激活并加重实验性自身免疫性脑脊髓炎小鼠的神经退行性变。

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

机构信息

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.

Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China.

出版信息

Neurosci Bull. 2024 Mar;40(3):283-292. doi: 10.1007/s12264-023-01111-z. Epub 2023 Sep 19.

DOI:10.1007/s12264-023-01111-z
PMID:37725245
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10912064/
Abstract

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/TGFβ 1/MAPK/Akt signaling pathways in the CNS of EAE mice. Consistently, Egr-1 siRNA promoted apoptosis but mitigated the activation of BDNF/TGFβ 1/MAPK/Akt signaling in SH-SY5Y cells. Our results revealed that Egr-1 is a crucial regulator of neuronal survival in EAE by regulating TGFβ 1-mediated signaling activation, implicating the important role of Egr-1 in the pathogenesis of multiple sclerosis as a potential novel therapy target.

摘要

早期生长反应蛋白 1（Egr-1）触发许多参与细胞生长、分化、突触可塑性和神经发生的基因的转录。然而，其在神经元存活和退化中的机制仍知之甚少。本研究表明，实验性自身免疫性脑脊髓炎（EAE）小鼠中枢神经系统（CNS）中 Egr-1 的 mRNA 和蛋白水平下调。Egr-1 基因敲除小鼠的 EAE 进展加重，表现为疾病严重程度和发生率增加；它还加重了神经元凋亡，这与 CNS 中 BDNF/TGFβ 1/MAPK/Akt 信号通路的激活减弱有关EAE 小鼠。一致地，Egr-1 siRNA 促进细胞凋亡，但减轻了 BDNF/TGFβ 1/MAPK/Akt 信号在 SH-SY5Y 细胞中的激活。我们的结果表明，Egr-1 通过调节 TGFβ 1 介导的信号激活，是 EAE 中神经元存活的关键调节剂，提示 Egr-1 在多发性硬化症发病机制中的重要作用，可能成为一种新的治疗靶点。

相似文献

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

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引用本文的文献

[1]
Fenofibrate maintains the integrity of the blood-brain barrier during cerebral ischemia-reperfusion injury by inhibiting Egr- 1.

In Vitro Cell Dev Biol Anim. 2025-5-27

本文引用的文献

[1]
Knockdown of NCOR2 Inhibits Cell Proliferation via BDNF/TrkB/ERK in NF1-Derived MPNSTs.

Cancers (Basel). 2022-11-24

[2]
Modulation of Ca signaling by antiapoptotic Bcl-2 versus Bcl-xL: From molecular mechanisms to relevance for cancer cell survival.

Biochim Biophys Acta Rev Cancer. 2022-11

[3]
HMGB1 from Astrocytes Promotes EAE by Influencing the Immune Cell Infiltration-Associated Functions of BMECs in Mice.

Neurosci Bull. 2022-11

[4]
Bioenergetic Impairment in the Neuro-Glia-Vascular Unit: An Emerging Physiopathology during Aging.

Aging Dis. 2021-12-1

[5]
Astrocytic YAP protects the optic nerve and retina in an experimental autoimmune encephalomyelitis model through TGF-β signaling.

Theranostics. 2021

[6]
Mice Heterozygous for the Sodium Channel Scn8a (Nav1.6) Have Reduced Inflammatory Responses During EAE and Following LPS Challenge.

Front Immunol. 2021

[7]
Disrupting the DNA Binding of EGR-1 with a Small-Molecule Inhibitor Ameliorates 2,4-Dinitrochlorobenzene-Induced Skin Inflammation.

J Invest Dermatol. 2021-7

[8]
Curcumin promotes osteogenic differentiation of human periodontal ligament stem cells by inducting EGR1 expression.

Arch Oral Biol. 2021-1

[9]
DEK-targeting aptamer DTA-64 attenuates bronchial EMT-mediated airway remodelling by suppressing TGF-β1/Smad, MAPK and PI3K signalling pathway in asthma.

J Cell Mol Med. 2020-12

[10]
Total flavonoids of astragalus attenuates experimental autoimmune encephalomyelitis by suppressing the activation and inflammatory responses of microglia via JNK/AKT/NFκB signaling pathway.

Phytomedicine. 2021-1

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