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并且与脂肪组织巨噬细胞浸润相关,并参与阻塞性睡眠呼吸暂停相关的代谢失调:来自生物信息学分析的证据。

and were correlated with adipose tissue macrophage infiltration and involved in obstructive sleep apnea related metabolic dysregulation: Evidence from bioinformatics analysis.

作者信息

Ming Xiaoping, Cai Weisong, Li Zhen, Yang Xiuping, Yang Minlan, Pan Dingyu, Chen Xiong

机构信息

Department of Otorhinolaryngology, Head, and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Sleep Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, China.

出版信息

Front Genet. 2023 Feb 27;14:1128139. doi: 10.3389/fgene.2023.1128139. eCollection 2023.

Abstract

Both obesity and obstructive sleep apnea (OSA) can lead to metabolic dysregulation and systemic inflammation. Similar to obesity, increasing evidence has revealed that immune infiltration in the visceral adipose tissue (VAT) is associated with obstructive sleep apnea-related morbidity. However, the pathological changes and potential molecular mechanisms in visceral adipose tissue of obstructive sleep apnea patients need to be further studied. Herein, by bioinformatics analysis and clinical validation methods, including the immune-related differentially expressed genes (IRDEGs) analysis, protein-protein interaction network (PPI), functional enrichment analysis, a devolution algorithm (CIBERSORT), spearman's correlation analysis, polymerase chain reaction (PCR), Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), we identified and validated 10 hub IRDEGs, the relative mRNA expression of four hub genes (), and the protein expression level of two hub genes ( and ) were consistent with the bioinformatics analysis results. Immune infiltration results further revealed that obstructive sleep apnea patients contained a higher proportion of pro-inflammatory M1 macrophages and a lower proportion of M2 macrophages. Spearman's correlation analysis showed that was positively correlated with M1 macrophages and was negatively correlated with M2 macrophages. and might play a vital role in the visceral adipose tissue homeostasis of obstructive sleep apnea patients. Their interaction with macrophages and involved pathways not only provides new insights for understanding molecular mechanisms but also be of great significance in discovering novel small molecules or other promising candidates as immunotherapies of OSA-associated metabolic complications.

摘要

肥胖和阻塞性睡眠呼吸暂停(OSA)均可导致代谢失调和全身炎症。与肥胖相似,越来越多的证据表明,内脏脂肪组织(VAT)中的免疫浸润与阻塞性睡眠呼吸暂停相关的发病率有关。然而,阻塞性睡眠呼吸暂停患者内脏脂肪组织中的病理变化和潜在分子机制仍需进一步研究。在此,通过生物信息学分析和临床验证方法,包括免疫相关差异表达基因(IRDEGs)分析、蛋白质-蛋白质相互作用网络(PPI)、功能富集分析、去卷积算法(CIBERSORT)、斯皮尔曼相关性分析、聚合酶链反应(PCR)、酶联免疫吸附测定(ELISA)和免疫组织化学(IHC),我们鉴定并验证了10个关键IRDEGs,4个关键基因的相对mRNA表达以及2个关键基因( 和 )的蛋白表达水平与生物信息学分析结果一致。免疫浸润结果进一步显示,阻塞性睡眠呼吸暂停患者中促炎性M1巨噬细胞比例较高,M2巨噬细胞比例较低。斯皮尔曼相关性分析表明, 与M1巨噬细胞呈正相关, 与M2巨噬细胞呈负相关。 和 可能在阻塞性睡眠呼吸暂停患者的内脏脂肪组织稳态中发挥重要作用。它们与巨噬细胞的相互作用及相关途径不仅为理解分子机制提供了新见解,而且在发现新型小分子或其他有前景的候选物作为OSA相关代谢并发症的免疫疗法方面具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f33/10009156/c9a3c50eb117/fgene-14-1128139-g001.jpg

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