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Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos.
Neural Regeneration Research ( IF 6.1 ) Pub Date : 2023-09-01 , DOI: 10.4103/1673-5374.366495
Bing-Qiang He 1 , Ai-Cheng Li 1 , Yu-Xuan Hou 1 , Hui Li 1 , Xing-Yuan Zhang 1 , Hui-Fei Hao 1 , Hong-Hua Song 1 , Ri-Xin Cai 1 , Ying-Jie Wang 1 , Yue Zhou 2 , Yong-Jun Wang 1
Affiliation  

The low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributors to the failure of sensory and motor functional recovery following spinal cord injury. Heat shock transcription factor 1 (HSF1), a master regulator of the heat shock response, plays neurogenetic and neuroprotective roles in the damaged or diseased central nervous system. However, the underlying mechanism has not been fully elucidated. In the present study, we used a gecko model of spontaneous nerve regeneration to investigate the potential roles of gecko HSF1 (gHSF1) in the regulation of neurite outgrowth and inflammatory inhibition of macrophages following spinal cord injury. gHSF1 expression in neurons and microglia at the lesion site increased dramatically immediately after tail amputation. gHSF1 overexpression in gecko primary neurons significantly promoted axonal growth by suppressing the expression of suppressor of cytokine signaling-3, and facilitated neuronal survival via activation of the mitogen-activated extracellular signal-regulated kinase/extracellular regulated protein kinases and phosphatidylinositol 3-kinase/protein kinase B pathways. Furthermore, gHSF1 efficiently inhibited the macrophage-mediated inflammatory response by inactivating IkappaB-alpha/NF-kappaB signaling. Our findings show that HSF1 plays dual roles in promoting axonal regrowth and inhibiting leukocyte inflammation, and provide new avenues of investigation for promoting spinal cord injury repair in mammals.

中文翻译:

热休克因子 1 促进神经突生长并抑制壁虎断脊髓中的炎症。

神经元的低内在生长能力和损伤诱导的抑制环境是脊髓损伤后感觉和运动功能恢复失败的主要原因。热休克转录因子 1 (HSF1) 是热休克反应的主要调节因子,在受损或患病的中枢神经系统中发挥神经发生和神经保护作用。然而,潜在的机制尚未完全阐明。在本研究中,我们使用自发神经再生的壁虎模型来研究壁虎 HSF1 (gHSF1) 在调节脊髓损伤后巨噬细胞的神经突生长和炎症抑制中的潜在作用。尾部截肢后,损伤部位神经元和小胶质细胞中的 gHSF1 表达立即显着增加。gHSF1 在壁虎原代神经元中的过表达通过抑制细胞因子信号转导抑制因子 3 的表达显着促进轴突生长,并通过激活有丝分裂原激活的细胞外信号调节激酶/细胞外调节蛋白激酶和磷脂酰肌醇 3-激酶/蛋白促进神经元存活激酶 B 途径。此外,gHSF1 通过灭活 IkappaB-α/NF-kappaB 信号有效抑制巨噬细胞介导的炎症反应。我们的研究结果表明,HSF1 在促进轴突再生和抑制白细胞炎症方面发挥双重作用,并为促进哺乳动物脊髓损伤修复提供了新的研究途径。并通过激活有丝分裂原激活的细胞外信号调节激酶/细胞外调节蛋白激酶和磷脂酰肌醇 3-激酶/蛋白激酶 B 通路促进神经元存活。此外,gHSF1 通过灭活 IkappaB-α/NF-kappaB 信号有效抑制巨噬细胞介导的炎症反应。我们的研究结果表明,HSF1 在促进轴突再生和抑制白细胞炎症方面发挥双重作用,并为促进哺乳动物脊髓损伤修复提供了新的研究途径。并通过激活有丝分裂原激活的细胞外信号调节激酶/细胞外调节蛋白激酶和磷脂酰肌醇 3-激酶/蛋白激酶 B 通路促进神经元存活。此外,gHSF1 通过灭活 IkappaB-α/NF-kappaB 信号有效抑制巨噬细胞介导的炎症反应。我们的研究结果表明,HSF1 在促进轴突再生和抑制白细胞炎症方面发挥双重作用,并为促进哺乳动物脊髓损伤修复提供了新的研究途径。
更新日期:2023-03-19
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