上睑下垂
炎症体
刺
炎症
内质网
脂多糖
先天免疫系统
未折叠蛋白反应
医学
免疫学
半胱氨酸蛋白酶1
细胞生物学
生物
免疫系统
工程类
航空航天工程
作者
Cao Yun,Xinghua Chen,Zijing Zhu,Zilv Luo,Yiqun Hao,Xueyan Yang,Jun Feng,Zongwei Zhang,Jijia Hu,Yonghong Jian,Jiefu Zhu,Wei Liang,Zhaowei Chen
标识
DOI:10.1038/s41419-024-06600-1
摘要
Abstract Recently, innate immunity and inflammation were recognized as the key factors for acute kidney injury (AKI) caused by sepsis, which is closely related to high mortality. Stimulator of interferon genes (STING) has emerged as a critical component of innate immune and inflammatory responses. However, the role of STING in the pathogenesis of septic AKI remains unclear. This study demonstrated that the STING was significantly activated in tubular cells induced by lipopolysaccharide (LPS) in vivo and in vitro. Tubule-specific STING knockout attenuated LPS-induced renal dysfunction and pathological changes. Mechanistically, the STING pathway promotes NOD-like receptor protein 3 (NLRP3) activation. STING triggers endoplasmic reticulum (ER) stress to induce mitochondrial reactive oxygen species (mtROS) overproduction, enhancing thioredoxin-interacting protein activation and association with NLRP3. Eventually, the NLRP3 inflammasome leads to tubular cell inflammation and pyroptosis. This study revealed the STING-regulated network and further identified the STING/ER stress/mtROS/NLRP3 inflammasome axis as an emerging pathway contributing to tubular damage in LPS-induced AKI. Hence, targeting STING may be a promising therapeutic strategy for preventing septic AKI.
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