南京医科大学学报（自然科学版）2025，Vol.45Issue(6)：786-797,12.DOI:10.7655/NYDXBNSN240702
scRNA-seq和Bulk RNA-seq联合分析揭示MTRNR2L1介导COPD进展中PANoptosis下调
Combined analysis of scRNA-seq and Bulk RNA-seq revealed that MTRNR2L1 mediated the downregulation of PANoptosis in COPD
摘要
Abstract
Objective:To explore the mechanism of MT-RNR2-like protein 1(MTRNR2L1)-mediated regulation of PANoptosis during the development of chronic obstructive pulmonary disease(COPD),and to provide new ideas for finding the pathogenesis of COPD.Methods:Bulk RNA sequencing(Bulk RNA-seq)data and single cell RNA sequencing(scRNA-Seq)data from COPD patients in Gene Expression Omnibus(GEO)were used to explore the cellular composition in COPD patients'lung tissues and to analyze the pathways involved in the development of the disease.PANoptosis was simulated in smoke/lipopolysaccharide(LPS)-exposed mice,and MTRNR2L1 and PANoptosis protein expression levels were assessed to clarify their roles in the development of COPD.Results:Bulk RNA-seq demonstrated the altered expression of T cell response-related genes between the COPD patients and the normal controls.scRNA-seq confirmed decreased CD8+T cells and increased epithelial cells in the COPD patients compared with controls.MTRNR2L1 was upregulated in COPD patient immune and epithelial cells,then those of controls PANoptosis-related genes were reduced in lungs,CD8+T cells and epithelial cells of COPD patients then those of controls:Smoke/LPS-exposed mouse lungs exhibit alveolar damage,increased expression of PANoptosis-related proteins,while MTRNR2L1 overexpression significantly inhibited cellular PANoptosis and downregulated the levels of ZBP1,Caspase-3,GSDMD,and MLKL.Conclusion:The differentially expressed genes in CD8+T cells and epithelial cells were enriched in pathways related to PANoptosis,suggesting the involvement of PANoptosis in the development of COPD.The process of PANoptosis in the onset and development of COPD was associated with increased expression of PANoptosis-related proteins.MTRNR2L1 exhibited an inhibitory effect on PANoptosis,and regulating PANoptosis may provide new therapeutic opportunities for reducing lung injury and improving lung ventilatory function.关键词
慢性阻塞性肺疾病/肺损伤/PANoptosis/单细胞RNA测序/批量RNA测序Key words
chronic obstructive pulmonary disease/lung damage/PANoptosis/single-cell RNA-seq/Bulk RNA-seq分类
临床医学引用本文复制引用
戈艳蕾,董爱英,刘铁军,付爱双,孙思怡,任泓沁,姚雪鑫,赵倩,李文强,陈伟彬,白静,喻昌利..scRNA-seq和Bulk RNA-seq联合分析揭示MTRNR2L1介导COPD进展中PANoptosis下调[J].南京医科大学学报（自然科学版）,2025,45(6):786-797,12.基金项目
唐山市人才资助项目(C202303026) （C202303026）
