Int J Biol Sci 2022; 18(2):661-674. doi:10.7150/ijbs.65861 This issue Cite

Research Paper

Regulation of lung epithelial cell senescence in smoking-induced COPD/emphysema by microR-125a-5p via Sp1 mediation of SIRT1/HIF-1a

Hao Wu1,2*, Huimin Ma2,3*, Lumin Wang1, Huazhong Zhang1, Lu Lu2,3, Tian Xiao2,3, Cheng Cheng2,3, Peiwen Wang2,3, Yi Yang2,3, Meng Wu2,3, Suhua Wang4, Jinsong Zhang1✉, Qizhan Liu2,3✉

1. Department of Emergency, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.
2. Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
3. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
4. Department of Toxicology, School of Public Health, Baotou Medical College, Baotou, 014040, Inner Mongolia, People's Republic of China.
*These authors contributed equally to this work.

Citation:
Wu H, Ma H, Wang L, Zhang H, Lu L, Xiao T, Cheng C, Wang P, Yang Y, Wu M, Wang S, Zhang J, Liu Q. Regulation of lung epithelial cell senescence in smoking-induced COPD/emphysema by microR-125a-5p via Sp1 mediation of SIRT1/HIF-1a. Int J Biol Sci 2022; 18(2):661-674. doi:10.7150/ijbs.65861. https://www.ijbs.com/v18p0661.htm
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Abstract

Graphic abstract

Chronic obstructive pulmonary disease (COPD) affects the health of more than 300 million people worldwide; at present, there is no effective drug to treat COPD. Smoking is the most important risk factor, but the molecular mechanism by which smoking causes the disease is unclear. The senescence of lung epithelial cells is related to development of COPD. Regulation of miRNAs is the main epigenetic mechanism related to aging. β-Galactose staining showed that the lung tissues of smokers have a higher degree of cellular senescence, and the expression of miR-125a-5p is high. This effect is obvious for smokers with COPD/emphysema, and there is a negative correlation between miR-125a-5p levels and values for forced expiratory volume in one second (FEV1)/forced vital capacity (FVC). After Balb/c mice were chronically exposed to various concentrations of cigarette smoke (CS), plethysmography showed that lung function was impaired, lung tissue senescence was increased, and the senescence-associated secretory phenotype (SASP) in bronchoalveolar lavage fluid was increased. For mouse lung epithelial (MLE)-12 cells treated with cigarette smoke extract (CSE), Sp1 and SIRT1 levels were low, HIF-1α acetylation levels were high, and cell senescence and secretion of SASP factors were elevated. Down-regulation of miR-125a-5p or up-regulation of Sp1 reversed these effects. In addition, compared with mice exposed to CS, knockdown of miR-125a-5p reduced lung epithelial cell senescence and COPD/emphysema. Therefore, in smoking-induced COPD, elevated miR-125a-5p participates in the senescence of lung epithelial cells through Sp1/SIRT1/HIF-1α. These findings provide evidence related to the pathogenesis of COPD/emphysema caused by chronic smoking.

Keywords: Smoking, Senescence, Chronic obstructive pulmonary disease, Emphysema, microRNAs


Citation styles

APA
Wu, H., Ma, H., Wang, L., Zhang, H., Lu, L., Xiao, T., Cheng, C., Wang, P., Yang, Y., Wu, M., Wang, S., Zhang, J., Liu, Q. (2022). Regulation of lung epithelial cell senescence in smoking-induced COPD/emphysema by microR-125a-5p via Sp1 mediation of SIRT1/HIF-1a. International Journal of Biological Sciences, 18(2), 661-674. https://doi.org/10.7150/ijbs.65861.

ACS
Wu, H.; Ma, H.; Wang, L.; Zhang, H.; Lu, L.; Xiao, T.; Cheng, C.; Wang, P.; Yang, Y.; Wu, M.; Wang, S.; Zhang, J.; Liu, Q. Regulation of lung epithelial cell senescence in smoking-induced COPD/emphysema by microR-125a-5p via Sp1 mediation of SIRT1/HIF-1a. Int. J. Biol. Sci. 2022, 18 (2), 661-674. DOI: 10.7150/ijbs.65861.

NLM
Wu H, Ma H, Wang L, Zhang H, Lu L, Xiao T, Cheng C, Wang P, Yang Y, Wu M, Wang S, Zhang J, Liu Q. Regulation of lung epithelial cell senescence in smoking-induced COPD/emphysema by microR-125a-5p via Sp1 mediation of SIRT1/HIF-1a. Int J Biol Sci 2022; 18(2):661-674. doi:10.7150/ijbs.65861. https://www.ijbs.com/v18p0661.htm

CSE
Wu H, Ma H, Wang L, Zhang H, Lu L, Xiao T, Cheng C, Wang P, Yang Y, Wu M, Wang S, Zhang J, Liu Q. 2022. Regulation of lung epithelial cell senescence in smoking-induced COPD/emphysema by microR-125a-5p via Sp1 mediation of SIRT1/HIF-1a. Int J Biol Sci. 18(2):661-674.

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