Possible mechanisms mediating apoptosis of bronchial epithelial cells in chronic obstructive pulmonary disease – A next-generation sequencing approach

Abstract

PurposeChronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease characterized by persistent airflow limitation. Apoptosis of pulmonary structural cells contributes to pulmonary destruction and dysfunction. This study aimed to explore the possible mechanisms underlying decreased cell proliferation and increased apoptosis of bronchial epithelial cells of COPD. Materials and methodsThe expression profiles of mRNAs and microRNAs in bronchial epithelial cells from a COPD patient and a normal subject were identified using next-generation sequencing (NGS) and analyzed using bioinformatic tools. ResultsWe identified 233 significantly upregulated and 204 significantly downregulated genes in COPD bronchial epithelial cells. The PI3K-Akt pathway was one of the most important dysregulated pathways in bronchial epithelial cells. We further identified that 3 genes involved in the PI3K-Akt signaling pathway, including IL6, F2R, and FGFR3, might be associated with inhibition of cell proliferation in bronchial epithelial cells, while 5 genes involved in the PI3K-Akt signaling pathway, including TLR4, IL6, F2R, FGFR3, and FGFR1, might be associated with apoptosis of bronchial epithelial cells. FGFR1 was also a predicted target for some up-regulated miRNAs in COPD bronchial epithelial cells, including hsa-miR-195-5p, hsa-miR-424-5p, and hsa-miR-6724-5p. ConclusionOur findings suggest PI3K-Akt signaling pathway plays an important role in COPD. We observed altered expression of apoptosis and cell proliferation-related genes that might contribute to the pathogenesis of COPD.