Zheng Nannan, Liu Xuanqi, Yang Ying, Liu Yifei, Yan Furong, Zeng Yiming, Cheng Yunfeng, Wu Duojiao, Chen Chengshui, Wang Xiangdong
Department of Respiratory Medicine, The First Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Jinshan Hospital Centre for Tumor Diagnosis and Therapy, Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.
Cell Biol Toxicol. 2023 Aug;39(4):1237-1256. doi: 10.1007/s10565-022-09743-z. Epub 2022 Jul 25.
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.
N-乙酰基转移酶10（NAT10）是一种核乙酰基转移酶，属于GNAT家族成员，在RNA稳定性、翻译过程以及细胞增殖中发挥关键作用。关于NAT10对肺上皮细胞增殖的调节作用知之甚少。我们首先分别研究了健康人和慢性阻塞性肺疾病、特发性肺纤维化、肺腺癌、癌旁组织及系统性硬化症患者的I型和II型肺泡上皮细胞、基底上皮细胞、纤毛上皮细胞、棒状上皮细胞以及杯状/黏液上皮细胞中NTA10 mRNA的表达情况。我们选择A549细胞作为肺泡上皮细胞的代表，或者选择具有不同遗传背景的气道上皮细胞H1299和H460细胞，研究NAT10下调的上皮细胞对高温、脂多糖、香烟烟雾提取物（CSE）、药物、辐射以及不同剂量的磷酸肌醇3激酶（PI3K）抑制剂的动态反应。我们还比较了肺泡上皮细胞和气道上皮细胞之间、NAT10下调或未下调的细胞之间、早期和晚期之间以及不同刺激条件下的转录组图谱。本研究表明，NAT10在人肺上皮细胞中的表达增加，且在不同上皮类型、刺激条件和疾病之间存在差异。敲低NAT10会改变上皮细胞的线粒体功能、对LPS、CSE或PI3K抑制剂的动态反应以及转录组表型。NAT10调节生物学表型，其行为更为复杂且依赖于多种信号通路。因此，NAT10相关信号通路可能是理解疾病以及开发新的生物标志物和靶点的新途径。
