雌激素相关受体α (ERRα)在小胶质细胞缺氧损伤中的作用

IF 1.5 3区 农林科学 Q2 VETERINARY SCIENCES Onderstepoort Journal of Veterinary Research Pub Date : 2022-03-01 DOI:10.2478/jvetres-2022-0009
Chaowei Deng, Tingting Zhu, S. Lian, Jianfa Wang, Rui Wu, Jia-san Zheng
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引用次数: 1

摘要

缺氧是脊髓损伤后常见的病理状态。雌激素相关受体α (estrogen-related receptor α, ERRα)作为能量代谢和线粒体功能的关键调节因子,在维持细胞稳态中起着重要作用。然而,其在缺氧脊髓小胶质细胞中的作用尚未得到充分阐述。本研究考察了这些细胞缺氧时受体的活性,并将其作为体外模型。材料与方法本研究将小胶质细胞(BV2)暴露于氯化钴作为缺氧模型,利用ERRα、XCT790和吡啶多[1,2-α]-嘧啶-4-one的逆激动剂调控受体的表达,探讨ERRα参与缺氧脊髓损伤(SCI)的相关机制。结果ERRα促进BV2细胞自噬,抑制缺氧条件下p38丝裂原活化蛋白激酶(MAPK)通路的激活和抗炎因子的表达。它还促进了纤维连接蛋白III型结构域蛋白5 (FNDC5)的表达。结论缺氧性脊髓损伤时,ERRα可能通过调节脊髓细胞自噬及p38MAPK/核因子- κ B细胞和FNDC5/脑源性神经营养因子信号通路维持脊髓细胞的稳态,有利于脊髓细胞的恢复。
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Estrogen-related Receptor α (ERRα) Functions in The Hypoxic Injury of Microglial Cells
Abstract Introduction Hypoxia is a common pathological condition after spinal cord injury. Oestrogen-related receptor alpha (ERRα), as a key regulator of energy metabolism and mitochondrial functions, plays an important role in maintaining cell homeostasis. However, its role in hypoxic spinal microglia has not been fully elaborated. This study investigated the receptor’s activity when these cells are hypoxic and used as an in vitro model. Material and Methods In this study, microglia (BV2) were exposed to cobalt chloride as a hypoxic model, and the inverse agonist of ERRα, XCT790, and pyrido[1,2-α]-pyrimidin-4-one were used to regulate the expression of the receptor to explore the ERRα-related mechanisms involved in hypoxic spinal cord injury (SCI). Results ERRα promoted autophagy in BV2 cells and inhibited the activation of the p38 mitogen-activated protein kinase (MAPK) pathway and the expression of anti-inflammatory factors under hypoxic conditions. It also promoted the expression of fibronectin type III domain containing protein 5 (FNDC5). Conclusion When a hypoxic SCI occurs, ERRα may maintain the homeostasis of spinal cord nerve cells by regulating autophagy and the p38MAPK/nuclear factor-kappa B cell and FNDC5/brain-derived neurotrophic factor signalling pathways, which are beneficial to the recovery of these cells.
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来源期刊
CiteScore
4.30
自引率
0.00%
发文量
13
审稿时长
16 weeks
期刊介绍: The Onderstepoort Journal of Veterinary Research, is the official publication of the Onderstepoort Veterinary Institute. While it considers submissions from any geographic region, its focus is on Africa and the infectious and parasitic diseases and disease vectors that affect livestock and wildlife on the continent.
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