Xie Rixi, Wang Fang
Geriatric Department, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou City, Jiangsu Province, China.
Geriatric Department, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou City, Jiangsu Province, China;
Allergol Immunopathol (Madr). 2025 Jan 1;53(1):146-152. doi: 10.15586/aei.v53i1.1218. eCollection 2025.
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation, airway obstruction, and lung damage, often triggered by cigarette smoke. Dysregulated autophagy and inflammation are key contributors to its progression. Although double-stranded RNA-binding protein Staufen homolog 1 (STAU1), a multifunctional protein primarily involved in mRNA transport and localization, is identified as a potential biomarker, its role in COPD pathogenesis remains unclear. This study investigates the effects of STAU1 knockdown on inflammation and autophagy in an COPD model. We found that STAU1 expression was significantly elevated in the COPD model. Knockdown of STAU1 led to a marked reduction in inflammation in cigarette smoke extract (CSE)-induced non-tumorigenic human bronchial epithelial cells (BEAS-2B). Additionally, STAU1 knockdown suppressed autophagy in CSE-induced BEAS-2B cells. Mechanistically, it inhibited the activation of the adenosine monophosphate-activated protein kinase-mechanistic target of rapamycin (AMPK/mTOR) pathway. In summary, STAU1 knockdown inhibits inflammation and autophagy by modulating the AMPK/mTOR axis. Targeting STAU1 could provide new avenues for the treatment of COPD.
慢性阻塞性肺疾病（COPD）的特征是慢性炎症、气道阻塞和肺损伤，通常由香烟烟雾引发。自噬失调和炎症是其进展的关键因素。尽管双链RNA结合蛋白Staufen同源物1（STAU1）是一种主要参与mRNA运输和定位的多功能蛋白，已被确定为一种潜在的生物标志物，但其在COPD发病机制中的作用仍不清楚。本研究调查了STAU1基因敲低对COPD模型中炎症和自噬的影响。我们发现，在COPD模型中STAU1表达显著升高。敲低STAU1可导致香烟烟雾提取物（CSE）诱导的非致瘤性人支气管上皮细胞（BEAS-2B）炎症明显减轻。此外，敲低STAU1可抑制CSE诱导的BEAS-2B细胞中的自噬。机制上，它抑制了腺苷单磷酸激活蛋白激酶-雷帕霉素机制性靶点（AMPK/mTOR）通路的激活。总之，敲低STAU1通过调节AMPK/mTOR轴抑制炎症和自噬。靶向STAU1可为COPD的治疗提供新途径。
