AIP1 通过NLRP12-ASC-Caspase-8 调节眼球血管新生 炎症酶介导的内皮质炎症
Yonghao Li1, Yimeng Sun2, Dasen Xie3
1Shenzhen Eye Hospital, Shenzhen Key Laboratory of Ophthalmology, Jinan University, Shenzhen, Guangdong, 518043, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|November 11, 2024
概括
研究人员确定了亡信号调节激酶1 (ASK1) - 相互作用蛋白-1 (AIP1) 作为一种关键因素,通过预防视网膜血管内皮细胞 (VEC) 中的炎症性亡来抑制病态眼球血管生成. 上调AIP1为视力丧失提供了一个新的治疗点.
科学领域:
- 眼科医生 眼科 眼科
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 病态眼球血管新生导致全球不可逆转的视力丧失.
- 目前对眼血管疾病的研究主要集中在亲血管性因素上,很少发现内源性抗血管性化合物.
- 连接炎症与病态眼球血管生成的机制在很大程度上是未知的.
研究的目的:
- 为了识别参与眼血管疾病的新型内源性抗血管原因子.
- 阐明炎症的作用,特别是 pyroptosis,在病态的眼睛血管生成.
- 调查针对视力威胁状况的已识别途径的治疗潜力.
主要方法:
- 在氧诱导视网膜病变 (OIR) 模型中使用单细胞RNA测序.
- 研究了视网膜血管内皮细胞 (VEC) 中的亡信号调节激酶1 (ASK1) 相互作用蛋白-1 (AIP1) 的功能.
- 分析了NLRP12-ASC-caspase-8炎症酶组合及其下游效应,包括气体皮质素D (GSDMD) 依赖性热.
主要成果:
- 鉴定出AIP1是一种特定于VEC的抗血管新生因子,可以抑制病态血管新生.
- 通过抑制NLRP12-ASC-caspase-8炎症体,AIP1可以防止视网膜VEC中的烧灭.
- 在OIR下降的AIP1促进了这种炎症体,导致GSDMD依赖的内皮质灭以及VEGF和IL-1β的释放,从而促进了新血管化.
- 针对NLRP12-CASP8-GSDMD轴和升级AIP1,减少了VEGF信号和新的船只形成.
结论:
- 一种涉及VEC pyroptosis的新型炎症途径驱动病态的眼球血管生成和视网膜新血管化.
- AIP1通过防止内皮皮质灭,作为这一过程的关键内源抑制剂.
- 向AIP1或烧亡途径为治疗与眼血管生成相关的视力丧失提供了一个有希望的治疗策略.
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