在糖尿病病中,PCSK9会引起炎症和cGAS/STING通路的激活
Zhicai Feng1,2, Xiangyu Liao1,2, Juan Peng1,2
1Department of Nephrology, the Third Xiangya Hospital, Central South University, Changsha, China.
概括
通过破坏线粒体DNA并激活cGAS/STING通路,PCSK9会在糖尿病病中引发炎. 抑制PCSK9或STING可以降低炎症,为糖尿病病提供潜在的治疗策略.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 在糖尿病病 (DN) 模型中,PCSK9水平升高与炎相关.
- 这种cGAS/STING通路与DN.的病原发生有关.
研究的目的:
- 研究PCSK9的促炎作用与DN.中的cGAS/STING通路之间的联系.
- 评估DN中PCSK9抑制的治疗潜力.
主要方法:
- 在体内使用PCSK9单克隆抗体 (mAbs) 和体内使用PCSK9siRNA来抑制PCSK9.
- 评估炎症标记物,损伤标记物和线粒体DNA (mtDNA) 损伤在高脂肪饮食/高脂肪菌素 (HFD/STZ) 治疗小鼠和人类-2 (HK-2) 细胞中.
- 研究了cGAS-STING通路激活和下游信号.
主要成果:
- 抑制PCSK9降低了损伤标志物 (血尿素,肌素,UACR) 和炎症性细胞因子 (IL-1β,MCP-1,TNF-α).
- 在DN模型中观察到mtDNA损伤增加和cGAS/STING通路激活.
- 抑制PCSK9和抑制STING (使用C-176) 显著降低了炎症.
结论:
- PCSK9通过导致mtDNA损伤和激活cGAS-STING通路来启动DNA中的炎症.
- 向PCSK9或STING代表了一种有前途的治疗方法,以减轻DN相关的炎症和进展.
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