HMGB1促进通过干眼诱导的溶酶体依赖细胞死亡,通过破坏溶酶体平衡来破坏溶酶体平衡
Xiaojuan Hu1,2, Jiayao Feng3, Chengjie Pan4
1National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Investigative ophthalmology & visual science
|February 4, 2025
概括
超性压力会增加核中的HMGB1,破坏溶酶体并导致干眼疾病 (DED). 减少HMGB1受保护的角膜细胞和减少DED症状.
科学领域:
- 眼科医生 眼科 眼科
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 超性压力是干眼病 (DED),炎症和亡的已知触发因素.
- 高流动性组盒1 (HMGB1) 表达因高压力而上调调,但其在DED病原和溶酶体平衡中的确切作用尚不清楚.
研究的目的:
- 调查HMGB1在溶酶体平衡中的作用及其对在高血压压力下干眼疾病发展的影响.
- 阐明HMGB1通过哪些机制影响角膜上皮细胞在超的条件下生存和功能.
主要方法:
- 使用活小鼠模型 (斯科波胺诱导的干眼) 和在高度条件下实验室人类角膜上皮细胞 (HCEC) 培养 (450mOsm).
- 采用免疫光学,核等离子体分离和电子显微镜来评估 lysosomal 功能,核 HMGB1 定位和细胞反应.
- 研究了通过RNAi对HMGB1敲击的效果以及溶酶体蛋白酶抑制剂的应用.
主要成果:
- 超性压力提高了HCEC中的核HMGB1的调节,破坏了 lysosomal 完整性并促进了HMGB1释放到细胞质中.
- 降低HMGB1的调控逆转了核至细胞质转移,改善了 lysosomal 功能,并减少了 cathepsin 泄漏.
- 在体内,甲素抑制降低了眼部炎症和干眼症状,而HMGB1敲击改善了细胞生存和自.
结论:
- 超位性压力诱导的HMGB1上调和核至细胞质转移导致溶酶体膜损伤,甲素释放和角膜上皮亡在DED.
- 降低HMGB1的调节改善了这些致病过程,突出显示HMGB1是干眼疾病的潜在治疗标.
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