He Yi-Jing, Chen Yi-Rong, Song Jia-Rui, Jiang Jin-Xiu, Liu Ting-Ting, Li Jia-Yao, Li Liu, Jia Jing
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China.
Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China.
Heliyon. 2024 May 13;10(10):e30967. doi: 10.1016/j.heliyon.2024.e30967. eCollection 2024 May 30.
Chronic obstructive pulmonary disease (COPD) and other respiratory diseases frequently present with airway mucus hypersecretion, which not only affects the patient's quality of life but also poses a constant threat to their life expectancy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, affects cell differentiation, tissue growth, and disease development. However, its role in airway mucus hypersecretion induced by COPD remains elusive. In this study, USP7 expression was significantly upregulated in airway epithelial samples from patients with COPD, and USP7 was also overexpressed in mouse lung and human airway epithelial cells in models of airway mucus hypersecretion. Inhibition of USP7 reduced the expression of nuclear factor kappa B (NF-κB), phosphorylated-NF-κB (p-NF-κB), and phosphonated inhibitor of nuclear factor kappa B (-IκBα), and alleviated the airway mucus hypersecretion and . Further research revealed that USP7 stimulated airway mucus hypersecretion through the activation of NF-κB nuclear translocation. In addition, the expression of mucin 5AC (MUC5AC) was suppressed by the NF-κB inhibitor erdosteine. These findings suggest that USP7 stimulates the NF-κB signaling pathway, which promotes airway mucus hypersecretion. This study identifies one of the mechanisms regulating airway mucus secretion and provides a new potential target for its prevention and treatment.
慢性阻塞性肺疾病（COPD）和其他呼吸系统疾病常伴有气道黏液高分泌，这不仅影响患者的生活质量，还对其预期寿命构成持续威胁。泛素特异性蛋白酶7（USP7）作为一种去泛素化酶，影响细胞分化、组织生长和疾病发展。然而，其在COPD诱导的气道黏液高分泌中的作用仍不清楚。在本研究中，COPD患者气道上皮样本中USP7表达显著上调，在气道黏液高分泌模型的小鼠肺和人气道上皮细胞中USP7也过表达。抑制USP7可降低核因子κB（NF-κB）、磷酸化核因子κB（p-NF-κB）和磷酸化核因子κB抑制因子（-IκBα）的表达，并减轻气道黏液高分泌。进一步研究表明，USP7通过激活NF-κB核转位刺激气道黏液高分泌。此外，NF-κB抑制剂厄多司坦可抑制黏蛋白5AC（MUC5AC）的表达。这些发现表明，USP7刺激NF-κB信号通路，促进气道黏液高分泌。本研究确定了调节气道黏液分泌的一种机制，并为其预防和治疗提供了一个新的潜在靶点。
