ERJ open research · 2025
Gene expression profiling of airway epithelium in Mycobacterium avium complex lung disease.
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Furuuchi Koji, Hijikata Minako, Seto Shintaro, Miyabayashi Akiko, Wakabayashi Keiko, Nakagawa Takayuki, Yoshida Tsutomu, Shimoda Kiyomi, Hiramatsu Miyako, Shiraishi Yuji, Morimoto Kozo, Keicho Naoto
Аннотация
BACKGROUND: Impaired mucociliary clearance is associated with nontuberculous mycobacterial lung disease (NTM-LD). While airway epithelial cells (AECs), which are essential for maintaining this defence mechanism, play a central role in NTM-LD pathogenesis, their in vivo gene expression in human NTM-LD remains unexplored. We investigated AEC gene expression using surgical specimens of Mycobacterium avium complex lung disease (MAC-LD) patients.
METHODS: We profiled gene expression of AECs from surgical specimens of age-matched female MAC-LD patients (n=7) and lung cancer patients (n=8), the latter serving as noninfectious controls. Differentially expressed genes identified through weighted gene coexpression network analysis were validated using quantitative reverse transcriptase PCR (qRT‒PCR) in an independent cohort (MAC-LD: n=19, Lung cancer: n=25). Associations between AEC gene expression and MAC-LD clinical phenotypes were also investigated.
RESULTS: We identified 54 upregulated and 4 downregulated genes in AECs from MAC-LD patients. In addition to immune-related genes enriched in antigen presentation, complement and coagulation cascades, neutrophil migration and the interleukin-17 signalling pathway, SLC26A4, which encodes the anion exchanger pendrin, was markedly upregulated (log2 fold change of 3.0, false discovery rate of 0.8×10-5). The increased expression of the selected genes CCL20, MMP9, C3 and SLC26A4 was validated, and their reproducibility was confirmed in the validation cohort. Among the 26 MAC-LD patients, the AEC gene expression level of MMP9 was significantly elevated in patients with cavitary lesions, whereas SLC26A4 expression was correlated with bronchiectasis severity.
CONCLUSIONS: SLC26A4, an anion exchanger, was markedly upregulated in MAC-LD AECs, alongside various immune-related genes. The associations between gene expression and key disease phenotypes suggest potential targets for novel therapeutics.
METHODS: We profiled gene expression of AECs from surgical specimens of age-matched female MAC-LD patients (n=7) and lung cancer patients (n=8), the latter serving as noninfectious controls. Differentially expressed genes identified through weighted gene coexpression network analysis were validated using quantitative reverse transcriptase PCR (qRT‒PCR) in an independent cohort (MAC-LD: n=19, Lung cancer: n=25). Associations between AEC gene expression and MAC-LD clinical phenotypes were also investigated.
RESULTS: We identified 54 upregulated and 4 downregulated genes in AECs from MAC-LD patients. In addition to immune-related genes enriched in antigen presentation, complement and coagulation cascades, neutrophil migration and the interleukin-17 signalling pathway, SLC26A4, which encodes the anion exchanger pendrin, was markedly upregulated (log2 fold change of 3.0, false discovery rate of 0.8×10-5). The increased expression of the selected genes CCL20, MMP9, C3 and SLC26A4 was validated, and their reproducibility was confirmed in the validation cohort. Among the 26 MAC-LD patients, the AEC gene expression level of MMP9 was significantly elevated in patients with cavitary lesions, whereas SLC26A4 expression was correlated with bronchiectasis severity.
CONCLUSIONS: SLC26A4, an anion exchanger, was markedly upregulated in MAC-LD AECs, alongside various immune-related genes. The associations between gene expression and key disease phenotypes suggest potential targets for novel therapeutics.