Ming-Ju Tsai1, Wei-An Chang2, Shu-Fang Jian3, Kuo-Feng Chang4, Chau-Chyun Sheu5, Po-Lin Kuo6. 1. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, No.100, Shih-Chuan 1st Rd., Kaohsiung, 807, Taiwan; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tz-You 1st Rd., Kaohsiung, 807, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, No.100, Shih-Chuan 1st Rd., Kaohsiung, 807, Taiwan; Department of Respiratory Therapy, School of Medicine, College of Medicine, Kaohsiung Medical University, No.100, Shih-Chuan 1st Rd., Kaohsiung, 807, Taiwan. Electronic address: SiegfriedTsai@gmail.com. 2. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, No.100, Shih-Chuan 1st Rd., Kaohsiung, 807, Taiwan; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tz-You 1st Rd., Kaohsiung, 807, Taiwan. Electronic address: 960215kmuh@gmail.com. 3. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, No.100, Shih-Chuan 1st Rd., Kaohsiung, 807, Taiwan. Electronic address: chienfang1216@gmail.com. 4. Welgene Biotech, Inc, Taipei, Taiwan. Electronic address: nickchang@welgene.com.tw. 5. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, No.100, Shih-Chuan 1st Rd., Kaohsiung, 807, Taiwan; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tz-You 1st Rd., Kaohsiung, 807, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, No.100, Shih-Chuan 1st Rd., Kaohsiung, 807, Taiwan; Department of Respiratory Therapy, School of Medicine, College of Medicine, Kaohsiung Medical University, No.100, Shih-Chuan 1st Rd., Kaohsiung, 807, Taiwan. Electronic address: sheucc@gmail.com. 6. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, No.100, Shih-Chuan 1st Rd., Kaohsiung, 807, Taiwan. Electronic address: kuopolin@seed.net.tw.
Abstract
PURPOSE: Chronic 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 METHODS: The 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. RESULTS: We 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. CONCLUSION: Our 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.
PURPOSE:Chronic 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 METHODS: The 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. RESULTS: We 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. CONCLUSION: Our 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.
Authors: Yang Liu; Kun Huang; Yahui Wang; Erqiang Hu; Benliang Wei; Zhaona Song; Yuqing Zou; Luanfeng Ge; Lina Chen; Wan Li Journal: Biomed Res Int Date: 2020-12-29 Impact factor: 3.411