N-乙酰转移酶10(NAT10),核乙酰转移酶和GNAT家族的成员,在RNA稳定性和翻译过程以及细胞增殖中起着关键作用。关于NAT10在肺上皮细胞增殖中的调节作用知之甚少。我们首先研究了NTA10mRNA在肺泡上皮I型和II型中的表达,基底,纤毛,俱乐部,和来自健康和慢性阻塞性肺疾病患者的杯状/粘液上皮,特发性肺纤维化,肺腺癌,肿瘤旁组织,和系统性硬化症,分别。我们选择A549细胞代表肺泡上皮或H1299和H460细胞作为具有不同遗传背景的气道上皮,并研究了NAT10下调上皮对高温的动态响应。脂多糖,吸烟提取物(CSE),毒品,辐射,和不同剂量的磷酸肌醇3-激酶(PI3K)抑制剂。我们还比较了肺泡上皮和气道上皮之间的转录组概况,在有或没有NAT10下调的细胞之间,在早期和晚期之间,在挑战之间。本研究表明,NAT10在人肺上皮中的表达增加,并且在上皮类型之间有所不同。挑战,和疾病。NAT10敲低改变上皮线粒体功能,对LPS的动态响应,CSE,或PI3K抑制剂,和转录组表型。NAT10调节生物表型,和行为更加复杂,并且依赖于多个信号通路。因此,NAT10相关的信号通路可以成为了解疾病和开发新的生物标志物和靶标的新替代方案。
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.