Early Growth Response Gene-1 Deficiency Interrupts TGFβ1 Signaling Activation and Aggravates Neurodegeneration in Experimental Autoimmune Encephalomyelitis Mice.
Yunyi LanXinyan HanFei HuangHailian ShiHui WuLiu YangZhibi HuXiaojun WuPublished in: Neuroscience bulletin (2023)
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.
Keyphrases
- signaling pathway
- cell cycle arrest
- high fat diet induced
- transforming growth factor
- pi k akt
- oxidative stress
- multiple sclerosis
- induced apoptosis
- transcription factor
- endoplasmic reticulum stress
- cell death
- cerebral ischemia
- cell proliferation
- epithelial mesenchymal transition
- wild type
- blood brain barrier
- insulin resistance
- stem cells
- gene expression
- type diabetes
- genome wide
- stress induced
- small molecule
- adipose tissue
- mesenchymal stem cells
- copy number
- cancer therapy
- drug delivery
- brain injury
- free survival