Department of Pediatrics, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.
Department of Surgery Ⅰ, Third Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
BMJ Open Respir Res. 2024 Apr 2;11(1):e002089. doi: 10.1136/bmjresp-2023-002089.
Asthma is a chronic disease affecting the lower respiratory tract, which can lead to death in severe cases. The cause of asthma is not fully known, so exploring its potential mechanism is necessary for the targeted therapy of asthma.
Asthma mouse model was established with ovalbumin (OVA). H&E staining, immunohistochemistry and ELISA were used to detect the inflammatory response in asthma. Transcriptome sequencing was performed to screen differentially expressed genes (DEGs). The role of KIF23 silencing in cell viability, proliferation and apoptosis was explored by cell counting kit-8, EdU assay and flow cytometry. Effects of KIF23 knockdown on inflammation, oxidative stress and pyroptosis were detected by ELISA and western blot. After screening KIF23-related signalling pathways, the effect of KIF23 on p53 signalling pathway was explored by western blot.
In the asthma model, the levels of caspase-3, IgG in serum and inflammatory factors (interleukin (IL)-1β, KC and tumour necrosis factor (TNF)-α) in serum and bronchoalveolar lavage fluid were increased. Transcriptome sequencing showed that there were 352 DEGs in the asthma model, and 7 hub genes including were identified. Knockdown of KIF23 increased cell proliferation and inhibited apoptosis, inflammation and pyroptosis of BEAS-2B cells induced by IL-13 in vitro. In vivo experiments verified that knockdown of inhibited oxidative stress, inflammation and pyroptosis to alleviate OVA-induced asthma mice. In addition, p53 signalling pathway was suppressed by KIF23 knockdown.
Knockdown of KIF23 alleviated the progression of asthma by suppressing pyroptosis and inhibited p53 signalling pathway.
哮喘是一种影响下呼吸道的慢性疾病，在严重情况下可导致死亡。哮喘的病因尚未完全明确，因此探索其潜在机制对于哮喘的靶向治疗是必要的。
用卵清蛋白（OVA）建立哮喘小鼠模型。通过 H&E 染色、免疫组织化学和 ELISA 检测哮喘中的炎症反应。进行转录组测序以筛选差异表达基因（DEGs）。通过细胞计数试剂盒-8、EdU 测定和流式细胞术探索 KIF23 沉默对细胞活力、增殖和凋亡的作用。通过 ELISA 和 Western blot 检测 KIF23 敲低对炎症、氧化应激和细胞焦亡的影响。筛选出 KIF23 相关信号通路后，通过 Western blot 探讨 KIF23 对 p53 信号通路的影响。
在哮喘模型中，血清中 caspase-3、IgG 水平以及血清和支气管肺泡灌洗液中炎症因子（白细胞介素（IL）-1β、KC 和肿瘤坏死因子（TNF）-α）水平升高。转录组测序显示哮喘模型中有 352 个 DEGs，鉴定出 7 个关键基因，包括 。体外实验中，KIF23 敲低增加了 BEAS-2B 细胞中由 IL-13 诱导的细胞增殖，抑制了细胞凋亡、炎症和细胞焦亡。体内实验验证了 KIF23 敲低通过抑制氧化应激、炎症和细胞焦亡来减轻 OVA 诱导的哮喘小鼠的病情。此外，KIF23 敲低抑制了 p53 信号通路。
KIF23 敲低通过抑制细胞焦亡和抑制 p53 信号通路来缓解哮喘的进展。
