Genomic evidence for dysregulated glutamine metabolism in the asthmatic airway epithelium.
Genomic evidence for dysregulated glutamine metabolism in the asthmatic airway epithelium.
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哮喘气道上皮谷氨酰胺代谢失调的基因组证据。
DOI：
10.1002/clt2.12178
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发表时间：
2022-07
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
作者：
气道上皮细胞（AECs）在肺组织稳态和疾病中起着关键作用。在哮喘中，AECs可通过分泌和调节多种介质，如花生四烯酸代谢物、生长因子、细胞因子和趋化因子，促进气道炎症和重塑的发展。正如最近的一篇综述所讨论的那样，aec中代谢途径的失调与哮喘高度相关。尽管谷氨酰胺代谢是多种生化途径的关键，但对其的研究仍然不足。在目前的研究中，我们试图确定与谷氨酰胺代谢相关的基因，这些基因在严重哮喘或辅助性T 2 （Th2）高哮喘患者中与健康对照组（hc）相比存在差异表达。我们的团队对两个公开的微阵列数据集进行了二次分析，这些数据集涉及新鲜的支气管刷牙样本。我们选择了这两个数据集，因为它们可在国家生物技术信息中心的基因表达综合数据库中获得（登录号为GSE43696和GSE67472），有充分记录的哮喘患者和气道采样程序的临床描述，包括hc样本，并得到同行评审的PubMed索引出版物的支持。3,4此外，两个数据集都有来自哮喘患者和hc患者的足够样本，这使我们能够在错误发现率（FDR）显著性调整后生成差异表达基因列表。第一个数据集（GSE43696）包括38名严重哮喘患者和20名hc患者。根据吸入或口服皮质类固醇的使用和/或气流限制，确定受试者患有严重哮喘。4这些样品使用全人类基因组微阵列4 x 44 K（安捷伦）进行处理。第二个数据集（GSE67472）包括40例Th2‐高哮喘患者和43例hc患者。根据AECs中三种白细胞介素(IL) - 13诱导基因的表达水平，确定受试者患有Th2‐高哮喘：骨膜素、丝氨酸肽酶抑制剂B2 （SERPINB2）和氯通道Ca2+激活1 （CLCA1）。在本例中，使用Human Genome U133 Plus 2.0 Array （affmetrix）对样品进行处理。对于哮喘组和HC组之间的比较，我们进行了适度的Benjamini - Hochberg t检验（FDR显著性调整），并确定了所有差异表达
To the Editor, Airway epithelial cells (AECs) play a critical role in lung tissue homeostasis and disease. In asthma, AECs can promote the development of airway inflammation and remodeling through the secretion and regulation of a wide array of mediators, such as arachidonic acid metabolites, growth factors, cytokines, and chemokines. 1 As discussed in a recent review, the dysregulation of metabolic pathways in AECs is highly relevant to asthma. 2 Even though glutamine metabolism is key to multiple biochemical pathways, it has remained understudied. In the present study, we sought to identify genes related to glutamine metabolism that are differentially expressed in patients with severe or T helper 2 (Th2)‐high asthma when compared to healthy controls (HCs).Our group performed a secondary analysis of two publicly available microarray datasets involving fresh bronchial brushing samples. We selected these two datasets as they were available in the National Center for Biotechnology Information's Gene Expression Omnibus (accession numbers GSE43696 and GSE67472), had well‐documented clinical description of asthmatics and airway sampling procedures, included samples from HCs, and were supported by peer‐reviewed PubMed‐indexed publications. 3, 4 In addition, both datasets had sufficient samples from asthmatics and HCs, which enabled us to generate a list of differentially expressed genes after false discovery rate (FDR) significance adjustment. The first dataset (GSE43696) included 38 individuals with severe asthma and 20 HCs. Subjects were determined to have severe asthma based on inhaled or oral corticosteroid use and/or airflow limitation. 4 These samples were processed using the Whole Human Genome Microarray 4 x 44 K (Agilent). The second dataset (GSE67472) included 40 patients with Th2‐high asthma and 43 HCs. Subjects were determined to have Th2‐high asthma based on the expression levels of three interleukin (IL)‐13‐inducible genes in AECs: periostin, serine peptidase inhibitor B2 (SERPINB2), and chloride channel Ca2+‐activated 1 (CLCA1). 3 In this case, the samples were processed using the Human Genome U133 Plus 2.0 Array (Affimetrix). For comparisons between the asthmatic and HC groups, we performed moderated Benjamini‐Hochberg t‐tests (with FDR significance adjustment) and identified all the differentially expressed
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影响因子：
5.6
作者：
Calvén J;Ax E;Rådinger M
通讯作者：
Rådinger M
DOI：
10.1164/ajrccm.161.3.9911005
发表时间：
2000-03-01
影响因子：
24.7
作者：
Hunt, JF;Fang, KZ;Gaston, B
通讯作者：
Gaston, B
DOI：
10.1152/ajplung.00122.2021
发表时间：
2021-07-01
影响因子：
4.9
作者：
Bartman, Colleen M.;Stelzig, Kimberly E.;Chiarella, Sergio E.
通讯作者：
Chiarella, Sergio E.
影响因子：
6.6
作者：
Phang JM
通讯作者：
Phang JM
影响因子：
3.5
作者：
Bogner AN;Stiers KM;Tanner JJ
通讯作者：
Tanner JJ