S100A9-TLR4轴通过阻断自的过程加剧了眼睛干燥
Lihong Liang1, Xue Yang1, Hao Zeng1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou, 510060, China.
Experimental eye research
|August 16, 2024
概括
S100A9上调驱动干眼病 (DED) 病原体通过阻断通过TLR4通路的自. 抑制S100A9或TLR4为DED提供了一个潜在的治疗策略,减少炎症和细胞死亡.
科学领域:
- 眼科医生 眼科 眼科
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 干眼病 (DED) 是一种普遍存在的眼表面疾病,具有复杂的病原性.
- 了解DED背后的分子机制对于开发有效的治疗方法至关重要.
研究的目的:
- 调查S100A9在干眼病 (DED) 病原发生中的作用.
- 探索S100A9作为DED的潜在治疗点.
主要方法:
- 来自DED.的小鼠眼腺切除 (LGE) 模型的公共单细胞RNA测序数据的分析.
- 使用免疫光学和西欧斑块验证S100A9表达.
- 通过TUNEL测定评估DED症状,包括液分泌和角膜染色,以及细胞死亡.
主要成果:
- 鉴定出S100A9是DED中高度可变的基因,在角膜上皮质表达增加.
- 通过改变LC3B-II/LC3B-I,SQSTM1和p-mTOR/mTOR水平表示的自阻塞在DED中观察到,并通过S100A9抑制 (paquinimod,PAQ) 逆转.
- PAQ降低了TLR4的调节,TLR4的抑制也缓解了自阻塞,导致DED症状的缓解,炎症和细胞死亡.
结论:
- 一个新的S100A9-TLR4自性阻塞途径与DED病变产生有关.
- 准S100A9或TLR4为治疗干眼疾病提供了一个有前途的治疗途径.
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