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高血糖诱导的甲素L成熟与糖尿病并发症和COVID-19死亡率有关
Qiong He1, Miao-Miao Zhao1, Ming-Jia Li1
1Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
糖尿病会增加甲素L (CTSL) 水平,从而增加感染SARS-CoV-2的风险. 高葡萄糖驱动CTSL成熟,将高血糖与糖尿病并发症和病毒易感性联系起来.
科学领域:
- 内分泌学 在内分泌学.
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 糖尿病是严重的COVID-19结果的主要风险因素.
- 甲素L (CTSL) 涉及糖尿病并发症和SARS-CoV-2的入口.
- 连接糖尿病,CTSL和COVID-19严重性的机制尚未完全理解.
研究的目的:
- 调查CATHEPSIN L (CTSL) 在糖尿病患者SARS-CoV-2感染中的作用.
- 阐明高血糖对CTSL活动和成熟的影响.
- 探索高血糖引起的CTSL和糖尿病并发症之间的联系.
主要方法:
- 测量了糖尿病和非糖尿病个体的血液CTSL水平和活性.
- 在不同的葡萄糖条件下,评估了野生型和CTSL淘汰细胞中的SARS-CoV-2感染.
- 使用了来自人类患者和Lepr-/-小鼠模型的肺组织样本.
- 通过ER-Golgi-lysosome路径研究了CTSL转位.
主要成果:
- 糖尿病患者表现出血中CTSL水平和活性升高,与高血糖相关.
- 高葡萄糖,而不是胰岛素,在野生类型细胞中增强了SARS-CoV-2感染.
- 在患有糖尿病的人类和小鼠的肺组织中,CTSL活性增加.
- 高葡萄糖促进CTSL成熟和溶酶体转位.
结论:
- 高血糖诱导的CTSL成熟是促进糖尿病中SARS-CoV-2感染的关键机制.
- 升高的CTSL活动有助于糖尿病并发症和增加COVID-19的严重程度.
- 准CTSL可能为患有病毒感染的糖尿病患者提供治疗策略.
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