在Nrf2/HMGB1/NF-κB轴调节冠状细胞亡和细胞外基质降解在骨关节炎
Acta biochimica et biophysica Sinica
|May 26, 2023
概括
Nrf2/HMGB1通路通过控制状细胞亡,炎症和ECM降解来调节关节炎. 较低的Nrf2和较高的HMGB1水平与OA发展有关.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 病理学 病理学 病理学
背景情况:
- 骨关节炎 (OA) 是一种退行性关节疾病,在这种疾病中,软骨细胞受到压力.
- 核因素红色素2相关因子2 (Nrf2) 作为压力反应的调节剂,在肌肉细胞中表现出抗氧化和抗炎性质.
研究的目的:
- 调查Nrf2及其下游途径在骨关节炎发展中的作用.
- 在OA的背景下,阐明Nrf2和高流动性组框1 (HMGB1) 之间的相互作用.
主要方法:
- 淋巴细胞用介质素-1β (IL-1β) 进行治疗,以诱导类似于OA的疾病.
- 操纵Nrf2和HMGB1水平 (过度表达/敲击) 来评估它们的影响.
- 分析包括细胞活力,细胞亡标志物,炎症因子表达,细胞外矩阵 (ECM) 成分水平和NF-κB通路激活.
- 在试验室和OA小鼠模型中使用了Tert-butylhydroquinone (TBHQ),Nrf2激活剂和复合HMGB1 (rHMGB1).
主要成果:
- IL-1β治疗抑制了Nrf2,降低了状细胞的活力,促进了亡和炎症,同时增加了矩阵降解标志物.
- Nrf2过度表达抵消了IL-1β诱导的有害影响.
- Nrf2通过与其促进体结合来抑制HMGB1的表达.
- 在小鼠中,HMGB1操纵逆转了Nrf2/TBHQ的保护作用,而rHMGB1则部分逆转了TBHQ的治疗作用.
- 甲状腺癌软骨显示Nrf2降低,HMGB1增加,细胞缩和炎症标志物.
结论:
- Nrf2/HMGB1轴被确定为冠状细胞亡,ECM降解,炎症和骨关节炎中NF-κB信号的新型调节器.
- 这一途径代表了骨关节炎治疗的潜在治疗标.
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