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肥胖患者的肺上皮细胞对 SARS-CoV-2 感染的控制能力受损。

Lung Epithelial Cells from Obese Patients Have Impaired Control of SARS-CoV-2 Infection.

机构信息

Meakins-Christie Laboratories, Research Institute of the McGill University Healthy Center, Montreal, QC H4A 3J1, Canada.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.

出版信息

Int J Mol Sci. 2023 Apr 4;24(7):6729. doi: 10.3390/ijms24076729.

Abstract

Obesity is known to increase the complications of the COVID-19 coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the exact mechanisms of SARS-CoV-2 infection in obese patients have not been clearly elucidated. This study aims to better understand the effect of obesity on the course of SARS-CoV-2 infection and identify candidate molecular pathways involved in the progression of the disease, using an in vitro live infection model and RNA sequencing. Results from this study revealed the enhancement of viral load and replication in bronchial epithelial cells (NHBE) from obese subjects at 24 h of infection (MOI = 0.5) as compared to non-obese subjects. Transcriptomic profiling via RNA-Seq highlighted the enrichment of lipid metabolism-related pathways along with , an inflammasome regulator, as a unique differentially expressed gene (DEG) in infected bronchial epithelial cells from obese subjects. Such findings correlated with altered cytokine and angiotensin-converting enzyme-2 (ACE2) expression during infection of bronchial cells. These findings provide a novel insight on the molecular interplay between obesity and SARS-CoV-2 infection. In conclusion, this study demonstrates the increased SARS-CoV-2 infection of bronchial epithelial cells from obese subjects and highlights the impaired immunity which may explain the increased severity among obese COVID-19 patients.

摘要

肥胖已知会增加由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起的 COVID-19 冠状病毒疾病的并发症。然而,肥胖患者中 SARS-CoV-2 感染的确切机制尚未明确阐明。本研究旨在使用体外活感染模型和 RNA 测序,更好地了解肥胖对 SARS-CoV-2 感染过程的影响,并确定参与疾病进展的候选分子途径。

这项研究的结果表明,与非肥胖受试者相比,肥胖受试者的支气管上皮细胞(NHBE)在感染 24 小时(MOI = 0.5)时病毒载量和复制增强。通过 RNA-Seq 进行的转录组分析突出了脂质代谢相关途径的富集,以及作为肥胖受试者感染的支气管上皮细胞中独特差异表达基因(DEG)的炎症小体调节剂。这些发现与感染支气管细胞期间细胞因子和血管紧张素转换酶 2(ACE2)表达的改变相关。

这些发现提供了肥胖与 SARS-CoV-2 感染之间分子相互作用的新见解。总之,本研究表明肥胖受试者的支气管上皮细胞中 SARS-CoV-2 感染增加,并强调了免疫受损,这可能解释了肥胖 COVID-19 患者病情加重的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9722/10095048/d165749050bf/ijms-24-06729-g001.jpg

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