Mechanism of glaucocalyxin a in alleviating asthma airway remodeling by inhibiting mitochondrial fission through targeting the TOP2A/CDK1 signaling pathway
10.13431/j.cnki.immunol.j.20250055
- VernacularTitle:蓝萼甲素通过靶向TOP2A/CDK1信号通路抑制线粒体裂变缓解哮喘气道重塑的作用机制
- Author:
Yihua PIAO
1
;
Ningpo DING
;
Fengxiang SHANG
;
Yilan SONG
;
Guanghai YAN
;
Zhiguang WANG
Author Information
1. 133002 延吉,吉林省过敏性常见疾病免疫与靶向研究重点实验室;133000 延吉,延边大学附属医院重症监护科
- Publication Type:Journal Article
- Keywords:
Glaucocalyxin A;
DNA topoisomerase Ⅱ α;
Cyclin-dependent kinase 1;
Mitochondrial fission;
Airway remodeling;
asthma
- From:
Immunological Journal
2025;41(6):369-376
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of Glaucocalyxin A(GLA)in inhibiting ovalbumin(OVA)-induced airway remodeling in asthmatic mice through the topoisomerase Ⅱ α(TOP2A)/cyclin-dependent kinase 1(CDK1)signaling pathway.Methods Forty Balb/c mice were randomly divided into 5 groups:the control group,the model group,the low-dose GLA group,the high-dose GLA group and the Dexamethasone group,with 8 mice in each group.The effect of GLA on airway remodeling was examined by immunohistochemical staining,ELISA and other methods,and bioinformatics methods were used to predict new targets of GLA.The action targets of TOP2A were screened using the STRING database,and the interaction relationship between the two was verified by co-immunoprecipitation.In vitro,GLA and siRNA were used to interfere with interleukin-4(IL-4)-stimulated human airway epithelial cells BEAS-2B.The expressions of TOP2A,epidermal growth factor receptor(EGFR),Integrin β1,focal adhesion kinase(FAK),β-catenin,CDK1 and DRP1 were detected by Western Blot.Results GLA intervention could significantly reduce OVA-induced asthma airway remodeling,airway smooth muscle thickening,collagen deposition around the airway,the number of eosinophils in alveolar lavage fluid,the expression of pro-inflammatory cytokines such as IL-4,and the level of serum IgE.The new target of GLA screened out was TOP2A,which was highly expressed in the lung tissue of the asthma airway remodeling model.GLA intervention could down-regulate its expression.In vitro,intervention with GLA and si-TOP2A could significantly down-regulate the expressions of IL-4-induced TOP2A,EGFR,Integrin β1,FAK and β-catenin.Further studies have found that TOP2A had an interaction relationship with CDK1.si-TOP2A could downregulate the expression of CDK1,and knockdown of CDK1 could significantly down-regulate the expression of phosphorylated DRP1.Conclusion GLA may alleviate asthma airway remodeling by targeting the TOP2A/CDK1 signaling pathway,providing experimental evidence for the clinical diagnosis and treatment of asthma airway remodeling in asthma.
