Bioinformatic analysis and experimental validation of the potential gene in the airway inflammation of steroid-resistant asthma

被引:3
|
作者
Wei, Chaochao [1 ,2 ,3 ,4 ]
Wang, Yang [5 ,6 ]
Hu, Chengping [5 ]
机构
[1] Hainan Gen Hosp, Dept Pulm & Crit Care Med, Haikou, Peoples R China
[2] Hainan Med Univ, Affiliated Hainan Hosp, Dept Pulm & Crit Care Med, Haikou, Peoples R China
[3] Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha, Peoples R China
[4] Hainan Med Univ, Key Lab Emergency & Trauma, Minist Educ, Haikou 571199, Peoples R China
[5] Cent South Univ, Xiangya Hosp, Dept Resp Med, Dept Resp & Crit Care Med, Changsha 410008, Hunan, Peoples R China
[6] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China
基金
海南省自然科学基金; 中国国家自然科学基金;
关键词
NF-KAPPA-B; RELATIVE CORTICOSTEROID INSENSITIVITY; DUAL-SPECIFICITY PHOSPHATASES; TH17; CELLS; NEUTROPHILIC INFLAMMATION; SMOOTH-MUSCLE; IFN-GAMMA; TNF-ALPHA; HYPERRESPONSIVENESS; PHENOTYPE;
D O I
10.1038/s41598-023-35214-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Steroid-resistant asthma is a troublesome clinical problem in public health. The pathogenesis of steroid-resistant asthma is complex and remains to be explored. In our work, the online Gene Expression Omnibus microarray dataset GSE7368 was used to explore differentially expressed genes (DEGs) between steroid-resistant asthma patients and steroid-sensitive asthma patients. Tissue-specific gene expression of DEGs was analyzed using BioGPS. The enrichment analyses were performed using GO, KEGG, and GSEA analysis. The protein-protein interaction network and key gene cluster were constructed using STRING, Cytoscape, MCODE, and Cytohubba. A steroid-resistant neutrophilic asthma mouse model was established using lipopolysaccharide (LPS) and ovalbumin (OVA). An LPS-stimulated J744A.1 macrophage model was prepared to validate the underlying mechanism of the interesting DEG gene using the quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A total of 66 DEGs were identified, most of which were present in the hematologic/immune system. Enrichment analysis displayed that the enriched pathways were the IL-17 signaling pathway, MAPK signal pathway, Toll-like receptor signaling pathway, and so on. DUSP2, as one of the top upregulated DEGs, has not been clearly demonstrated in steroid-resistant asthma. In our study, we observed that the salubrinal administration (DUSP2 inhibitor) reversed neutrophilic airway inflammation and cytokine responses (IL-17A, TNF-alpha) in a steroid-resistant asthma mouse model. We also found that salubrinal treatment reduced inflammatory cytokines (CXCL10 and IL-1 beta) in LPS-stimulated J744A.1 macrophages. DUSP2 may be a candidate target for the therapy of steroid-resistant asthma.
引用
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页数:14
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