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cGAS inhibition alleviates Alu RNA-induced immune responses and cytotoxicity in retinal pigmented epithelium

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机构: [1]Capital Med Univ, Beijing Tongren Eye Ctr, Beijing Tongren Hosp, Beijing 100730, Peoples R China [2]Army Med Univ, Sergeant Sch, Affiliated Hosp, Dept Emergency Med, Shijiazhuang 050000, Hebei, Peoples R China
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关键词: RPE AMD GA cGAS Alu RNA EGCG RSVL

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Background The degeneration of retinal pigmented epithelium (RPE) cells results in severe diseases, such as age-related macular degeneration (AMD) that causes blindness in millions of individuals. Results We report that targeting GMP-AMP (cGAMP) synthase (cGAS) alleviates Alu RNA-induced immune responses and cytotoxicity in RPE. We find that the deletion of cGAS in RPE inhibits the Alu RNA-stimulated interferon production. cGAS deficiency also protects RPE from cell death triggered by Alu RNA. Importantly, two natural chemicals, epigallocatechin gallate (EGCG) and resveratrol (RSVL), are effective in suppressing the immunogenic and cytotoxic effect of Alu RNA in RPE. Conclusions Our findings further demonstrate the crucial role of cGAS in the Alu RNA-induced RPE damage and present EGCG and RSVL as potential therapies for AMD and other RPE degeneration-related conditions.

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出版当年[2021]版:
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学
最新[2025]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
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出版当年[2020]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
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Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

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第一作者机构: [1]Capital Med Univ, Beijing Tongren Eye Ctr, Beijing Tongren Hosp, Beijing 100730, Peoples R China
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