敲除 KIF23 可通过抑制脓毒症缓解哮喘进展

IF 3.6 3区 医学 Q1 RESPIRATORY SYSTEM BMJ Open Respiratory Research Pub Date : 2024-04-01 DOI:10.1136/bmjresp-2023-002089
Xingyu Rao, Zicheng Lei, Huifang Zhu, Kaiyuan Luo, Chaohua Hu
{"title":"敲除 KIF23 可通过抑制脓毒症缓解哮喘进展","authors":"Xingyu Rao, Zicheng Lei, Huifang Zhu, Kaiyuan Luo, Chaohua Hu","doi":"10.1136/bmjresp-2023-002089","DOIUrl":null,"url":null,"abstract":"Background 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. Method 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. Results 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 KIF23 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 KIF23 inhibited oxidative stress, inflammation and pyroptosis to alleviate OVA-induced asthma mice. In addition, p53 signalling pathway was suppressed by KIF23 knockdown. Conclusion Knockdown of KIF23 alleviated the progression of asthma by suppressing pyroptosis and inhibited p53 signalling pathway. Data are available in a public, open access repository. The datasets used and/or analysed during the current study have been uploaded to NCBI SRA database (<https://www.ncbi.nlm.nih.gov/sra/PRJNA1019821>).","PeriodicalId":9048,"journal":{"name":"BMJ Open Respiratory Research","volume":"6 1","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Knockdown of KIF23 alleviates the progression of asthma by inhibiting pyroptosis\",\"authors\":\"Xingyu Rao, Zicheng Lei, Huifang Zhu, Kaiyuan Luo, Chaohua Hu\",\"doi\":\"10.1136/bmjresp-2023-002089\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background 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. Method 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. Results 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 KIF23 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 KIF23 inhibited oxidative stress, inflammation and pyroptosis to alleviate OVA-induced asthma mice. In addition, p53 signalling pathway was suppressed by KIF23 knockdown. Conclusion Knockdown of KIF23 alleviated the progression of asthma by suppressing pyroptosis and inhibited p53 signalling pathway. Data are available in a public, open access repository. The datasets used and/or analysed during the current study have been uploaded to NCBI SRA database (<https://www.ncbi.nlm.nih.gov/sra/PRJNA1019821>).\",\"PeriodicalId\":9048,\"journal\":{\"name\":\"BMJ Open Respiratory Research\",\"volume\":\"6 1\",\"pages\":\"\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMJ Open Respiratory Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/bmjresp-2023-002089\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMJ Open Respiratory Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/bmjresp-2023-002089","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0

摘要

背景 哮喘是一种影响下呼吸道的慢性疾病,严重时可导致死亡。哮喘的病因尚不完全清楚,因此探索其潜在机制对于哮喘的靶向治疗非常必要。方法 用卵清蛋白(OVA)建立哮喘小鼠模型。采用 H&E 染色、免疫组化和 ELISA 检测哮喘的炎症反应。通过转录组测序筛选差异表达基因(DEGs)。通过细胞计数试剂盒-8、EdU测定和流式细胞术探讨了KIF23沉默在细胞活力、增殖和凋亡中的作用。通过酶联免疫吸附试验(ELISA)和免疫印迹法检测了 KIF23 基因敲除对炎症、氧化应激和热休克的影响。在对 KIF23 相关信号通路进行筛选后,通过 Western 印迹探讨了 KIF23 对 p53 信号通路的影响。结果 在哮喘模型中,血清中的 caspase-3、IgG 以及血清和支气管肺泡灌洗液中的炎症因子(白细胞介素(IL)-1β、KC 和肿瘤坏死因子(TNF)-α)水平均升高。转录组测序显示,哮喘模型中有 352 个 DEGs,并确定了包括 KIF23 在内的 7 个中心基因。在体外实验中,KIF23的敲除增加了细胞增殖,抑制了IL-13诱导的BEAS-2B细胞的凋亡、炎症和裂解。体内实验证实,敲除KIF23可抑制氧化应激、炎症和脓毒症,从而缓解OVA诱导的小鼠哮喘。此外,KIF23 的敲除还抑制了 p53 信号通路。结论 敲除 KIF23 可抑制脓毒症并抑制 p53 信号通路,从而缓解哮喘的恶化。数据可在公开、开放的资源库中获取。本研究中使用和/或分析的数据集已上传到 NCBI SRA 数据库()。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Knockdown of KIF23 alleviates the progression of asthma by inhibiting pyroptosis
Background 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. Method 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. Results 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 KIF23 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 KIF23 inhibited oxidative stress, inflammation and pyroptosis to alleviate OVA-induced asthma mice. In addition, p53 signalling pathway was suppressed by KIF23 knockdown. Conclusion Knockdown of KIF23 alleviated the progression of asthma by suppressing pyroptosis and inhibited p53 signalling pathway. Data are available in a public, open access repository. The datasets used and/or analysed during the current study have been uploaded to NCBI SRA database ().
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
BMJ Open Respiratory Research
BMJ Open Respiratory Research RESPIRATORY SYSTEM-
CiteScore
6.60
自引率
2.40%
发文量
95
审稿时长
12 weeks
期刊介绍: BMJ Open Respiratory Research is a peer-reviewed, open access journal publishing respiratory and critical care medicine. It is the sister journal to Thorax and co-owned by the British Thoracic Society and BMJ. The journal focuses on robustness of methodology and scientific rigour with less emphasis on novelty or perceived impact. BMJ Open Respiratory Research operates a rapid review process, with continuous publication online, ensuring timely, up-to-date research is available worldwide. The journal publishes review articles and all research study types: Basic science including laboratory based experiments and animal models, Pilot studies or proof of concept, Observational studies, Study protocols, Registries, Clinical trials from phase I to multicentre randomised clinical trials, Systematic reviews and meta-analyses.
期刊最新文献
Trends of mortality from chronic respiratory diseases by sex and ethnicity in the USA: a secular analysis from 1979 to 2021 using data from death certificates. Firefighters' occupational exposure to air pollution: impact on COPD and asthma-study protocol. Risk factors for incidence of interstitial lung disease in patients with rheumatoid arthritis: a systematic review and meta-analysis. Pleural effusion in acute pulmonary embolism: characteristics and relevance. Pim1 inactivating induces RUNX3 upregulation that improves/alleviates airway inflammation and mucus hypersecretion in vitro and in vivo.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1