Abstract
N-acetyltransferase 10 (NAT10), a nuclear acetyltransferase and a member of the GNAT family, plays critical roles in RNA stability and translation processes as well as cell proliferation. Little is known about regulatory effects of NAT10 in lung epithelial cell proliferation. We firstly investigated NTA10 mRNA expression in alveolar epithelial types I and II, basal, ciliated, club, and goblet/mucous epithelia from heathy and patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, lung adenocarcinoma, para-tumor tissue, and systemic sclerosis, respectively. We selected A549 cells for representative of alveolar epithelia or H1299 and H460 cells as airway epithelia with different genetic backgrounds and studied dynamic responses of NAT10-down-regulated epithelia to high temperature, lipopolysaccharide, cigarette smoking extract (CSE), drugs, radiation, and phosphoinositide 3-kinase (PI3K) inhibitors at various doses. We also compared transcriptomic profiles between alveolar and airway epithelia, between cells with or without NAT10 down-regulation, between early and late stages, and between challenges. The present study demonstrated that NAT10 expression increased in human lung epithelia and varied among epithelial types, challenges, and diseases. Knockdown of NAT10 altered epithelial mitochondrial functions, dynamic responses to LPS, CSE, or PI3K inhibitors, and transcriptomic phenomes. NAT10 regulates biological phenomes, and behaviors are more complex and are dependent upon multiple signal pathways. Thus, NAT10-associated signal pathways can be a new alternative for understanding the disease and developing new biomarkers and targets.
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The work was supported by the Operation Funding of Shanghai Institute of Clinical Bioinformatics and Shanghai Engineering and Technology Center for Artificial Intelligence of Lung and Heart Diseases from Zhongshan Hospital and the National Nature Science Foundation of China (81873409).
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NZ led the full activities of the project and preparation of manuscript writing and editing; XL, YY, YL, and FY contributed to parts of experimental studies or data analyses; YZ, YC, DW, CC, and XW were responsible for study design, discussion, funding, and preparation of manuscript. All authors read and approved the final manuscript.
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Nannan Zheng, Xuanqi Liu, Ying Yang, Yifei Liu, and Furong Yan contributed to this article equally as the first author.
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Zheng, N., Liu, X., Yang, Y. et al. Regulatory roles of NAT10 in airway epithelial cell function and metabolism in pathological conditions. Cell Biol Toxicol 39, 1237–1256 (2023). https://doi.org/10.1007/s10565-022-09743-z
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DOI: https://doi.org/10.1007/s10565-022-09743-z