[Overexpressing NDUFA13 and CRIP1 improves B cell injury and lung Lesions in COPD mouse models]

To identify B cell-associated biomarkers in chronic obstructive pulmonary disease (COPD) using bioinformatics and explore their diagnostic and therapeutic potential.

Based on the GEO database, differential expression analysis, WGCNA, scRNA-seq, ROC curve analysis, and Mendelian randomization analysis were performed to screen B cell-related biomarkers. Twenty ICR mice were divided equally into control and COPD groups, and COPD model was established using lipopolysaccharide (LPS) combined with cigarette smoke exposure to verify biomarker expression. Cultured murine B lymphoma CH12.LX cells were stimulated with 1 μg/mL LPS and transfected with plasmids overexpressing CRIP1 or NDUFA13 or with a negative control plasmid, and the changes in protein expressions of NDUFB8, MTCO1, ATP5A and ACTB were examined with Western blotting. CCK-8 assay and flow cytometry were used to analyze the viability and apoptosis of murine lung epithelial cells co-cultured with the treated CH12.LX cells, respectively.

Two protective factors, namely NDUFA13 (OR=0.2598) and CRIP1 (OR=0.2690; P<0.0001), were identified as the key B cell-associated biomarkers in COPD. In the mouse models of COPD, the expressions of NDUFA13 and CRIP1 were significantly downregulated in the lung tissues at both the transcriptional and protein levels. In CH12.LX cells, stimulation with LPS significantly lowered the protein expressions of NDUFA13, CRIP1, NDUFB8, MTCO1 and ATP5A. Overexpression of CRIP1 or NDUFA13 effectively inhibited LPS-induced inflammatory responses and oxidative stress in CH12.LX cells, and promoted the viability and suppressed apoptosis of lung epithelial cells co-cultured with CH12.LX cells.

NDUFA13 and CRIP1 are B cell-associated protective biomarkers in COPD with potential diagnostic values for COPD.