Screening of mitochondria-targeting markers in alveolar macrophages of silicosis patients based on bioinformatics analysis
10.19405/j.cnki.issn1000-1492.2024.10.019
- VernacularTitle:基于生物信息学分析筛选矽肺患者肺泡巨噬细胞中线粒体靶向标志物
- Author:
Hongming CHENG
1
;
Hailan HE
;
Yuan WANG
;
Xiaohui HAO
;
Hongli WANG
;
Heliang LIU
Author Information
1. 华北理工大学公共卫生学院,唐山 063210
- Keywords:
silicosis;
macrophage;
mitochondrial fission;
mitochondrial fusion;
bioinformatics
- From:
Acta Universitatis Medicinalis Anhui
2024;59(10):1828-1834,1841
- CountryChina
- Language:Chinese
-
Abstract:
Objective To screen mitochondria-targeting differential genes in alveolar macrophages of silicosis pa-tients and explore the role of mitochondrial homeostasis in alveolar macrophages of silicosis patients.Methods High-throughput sequencing dataset GSE174725 was downloaded,and differentially expressed genes were screened with R software and P＜0.05,|LogFC|＞1,and then intermixed with mitochondrial gene bank MitoCarta3.0 to obtain mitochondria-targeted differentially expressed genes.Then enrichment analysis was carried out to obtain the biological processes and pathways involved in differential genes,and the protein-protein interaction network was constructed.In addition,alveolar macrophages from silicosis patients and healthy controls were collected,the ex-pression levels of differential genes were detected by RT-qPCR,and the expressions of mitochondria-related factors mitochondrial fusion protein 1(MFN1),optic atrophy 1(OPA1)and dynamin-related protein 1(DRP1)in alveolar macrophages of silicosis patients were investigated by Western blot.Results A total of 204 differentially expressed genes were screened in silicosis patients,among which 62 differentially expressed genes were up-regulated,142 dif-ferentially expressed genes were down-regulated,and 22 differentially expressed genes were mitochondria-targeted.The concentration analysis of differentially expressed genes targeted by mitochondria showed that the cell compo-nents mainly enriched included mitochondrial membrane,endoplasmic membrane side components,etc.The bio-logical processes mainly enriched included mitochondrial electron transfer from NADH to ubiquinone,inflammatory response,immune response,etc.The main molecular functions enriched included the rotation mechanism of proton transport ATP synthase activity,NADH dehydrogenase activity,chemokine activity,etc.KEGG enrichment analy-sis mainly focused on the involvement in chemical carcinogenesis-ROS,IL-17 signaling pathway,toll-like receptor signaling pathway,chemokine signaling pathway,TNF signaling pathway,etc.In addition,RT-qPCR results showed that the expressions of mitochondrial cytochrome coxidase 1,mitochondrial cytochrome coxidase 2,mito-chondrial cytochrome coxidase 3,mitochondrially encoded NADH dehydrogenase 1,mitochondrially encoded NADH dehydrogenase 3,mitochondrially encoded NADH dehydrogenase 5,superoxide dismutase and mitochondri-ally encoded ATP synthase 6 gene were down-regulated in silicosis patients(P＜0.05).Western blot and RT-qPCR results showed that,in silicosis patients,the expression of MFN1 and OPA1 decreased(P＜0.05),while the expression of DRP1 increased(P＜0.05).Conclusion Bioinformatics analysis and validation,eight mito-chondrial targeted differential genes(MT-CO1,MT-C02,MT-CO3,MT-ND1,MT-ND3,MT-ND5,SOD and MT-ATP6)were finally obtained,which were enriched in mitochondrial respiratory chain and oxidative stress pathways and might play an important role in the process of silicosis.
- Full text:2024122513470184357基于生物信息学分析筛选矽肺...巨噬细胞中线粒体靶向标志物_程鸿明.pdf
