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iTRAQ 蛋白质组学分析揭示了尘螨相关哮喘经皮下变应原免疫治疗后的潜在调控网络。

iTRAQ‑based proteomic analysis reveals potential regulatory networks in dust mite‑related asthma treated with subcutaneous allergen immunotherapy.

机构信息

Department of Pediatrics, Foshan Maternal and Children's Hospital Affiliated to Southern Medical University, Foshan, Guangdong 528000, P.R. China.

Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, P.R. China.

出版信息

Mol Med Rep. 2020 Nov;22(5):3607-3620. doi: 10.3892/mmr.2020.11472. Epub 2020 Sep 1.

Abstract

Asthma is one of the most common childhood chronic diseases worldwide. Subcutaneous immunotherapy (SCIT) is commonly used in the treatment of house dust mite (HDM)‑related asthma in children. However, the therapeutic mechanism of SCIT in asthma remains unclear. The present study aimed to investigate the molecular biomarkers associated with HDM‑related asthma in asthmatic children prior and subsequent to SCIT treatment compared with those in healthy children via proteomic analysis. The study included a control group (30 healthy children), ‑Treatment group (30 children with HDM‑related allergic asthma) and +Treatment group (30 children with HDM‑related allergic asthma treated with SCIT). An isobaric labeling with relative and absolute quantification‑based method was used to analyze serum proteome changes to detect differentially expressed proteins, while functional enrichment and protein‑protein interaction network analysis were used to select candidate biomarkers. A total of 72 differentially expressed proteins were detected in the ‑Treatment, +Treatment and control groups. A total of 33 and 57 differentially expressed proteins were observed in the ‑Treatment vs. control and +Treatment vs. control groups, respectively. Through bioinformatics analysis, 5 candidate proteins [keratin 1 (KRT1), apolipoprotein B (APOB), fibronectin 1, antithrombin III (SERPINC1) and α‑1‑antitrypsin (SERPINA1)] were selected for validation by western blotting; among them, 4 proteins (KRT1, APOB, SERPINC1 and SERPINA1) showed robust reproducibility in asthma and control samples. This study illustrated the changes in proteome regulation following SCIT treatment for asthma. The 4 identified proteins may serve as potential biomarkers prior and subsequent to SCIT treatment, and help elucidate the molecular regulation mechanisms of SCIT to treat HDM‑related asthma.

摘要

哮喘是全球最常见的儿童慢性疾病之一。皮下免疫疗法(SCIT)常用于治疗儿童尘螨(HDM)相关哮喘。然而,SCIT 治疗哮喘的确切机制尚不清楚。本研究旨在通过蛋白质组学分析,比较哮喘儿童在 SCIT 治疗前后与健康儿童之间与 HDM 相关哮喘相关的分子生物标志物。该研究包括对照组(30 名健康儿童)、-治疗组(30 名患有 HDM 相关过敏性哮喘的儿童)和+治疗组(30 名接受 SCIT 治疗的患有 HDM 相关过敏性哮喘的儿童)。采用基于相对和绝对定量的同位素标记技术分析血清蛋白质组变化,以检测差异表达蛋白,同时进行功能富集和蛋白质-蛋白质相互作用网络分析,以选择候选生物标志物。在 -治疗组、+治疗组和对照组中检测到 72 个差异表达蛋白。在 -治疗组与对照组和+治疗组与对照组比较中,分别观察到 33 个和 57 个差异表达蛋白。通过生物信息学分析,选择了 5 个候选蛋白[角蛋白 1(KRT1)、载脂蛋白 B(APOB)、纤维连接蛋白 1、抗凝血酶 III(SERPINC1)和α-1-抗胰蛋白酶(SERPINA1)]进行 Western 印迹验证;其中,4 个蛋白(KRT1、APOB、SERPINC1 和 SERPINA1)在哮喘和对照样本中具有稳健的重现性。本研究阐明了 SCIT 治疗哮喘后蛋白质组调控的变化。这 4 种鉴定出的蛋白可能作为 SCIT 治疗前后的潜在生物标志物,有助于阐明 SCIT 治疗 HDM 相关哮喘的分子调控机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe2/7533450/397696ab8acb/MMR-22-05-3607-g00.jpg

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