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}
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 ().
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.