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Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease

Dermatomyositis (DM), an inflammatory disorder, is often associated with interstitial lung disease (ILD). However, the underlying mechanism remains unclear. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of differentially expressed genes (DEGs) in patients with...

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Autores principales: Chen, Juan, Zhang, Ruixian, Xie, Min, Luan, Chunyan, Li, Xiaolan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685457/
https://www.ncbi.nlm.nih.gov/pubmed/34938325
http://dx.doi.org/10.3389/fgene.2021.784215
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author Chen, Juan
Zhang, Ruixian
Xie, Min
Luan, Chunyan
Li, Xiaolan
author_facet Chen, Juan
Zhang, Ruixian
Xie, Min
Luan, Chunyan
Li, Xiaolan
author_sort Chen, Juan
collection PubMed
description Dermatomyositis (DM), an inflammatory disorder, is often associated with interstitial lung disease (ILD). However, the underlying mechanism remains unclear. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of differentially expressed genes (DEGs) in patients with dermatomyositis-associated interstitial lung disease (DM-ILD) and healthy controls. A total of 2,018 DEGs were identified between DM-ILD and healthy blood samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that DEGs were mainly involved in immune- and inflammatory-related biological processes and pathways. Disease ontology (DO) enrichment analysis identified 35 candidate key genes involved in both skin and lung diseases. Meanwhile, a total of 886 differentially expressed alternative splicing (AS) events were found between DM-ILD and healthy blood samples. After overlapping DEGs with differential AS genes, the plasminogen activator and urokinase receptor (PLAUR) involved in immune-related biological processes and complement and coagulation cascades was screened and identified as the most important gene associated with DM-ILD. The protein–protein interaction (PPI) network revealed that PLAUR had interactions with multiple candidate key genes. Moreover, we observed that there were significantly more neutrophils and less naive B cells in DM-ILD samples than in healthy samples. And the expression of PLAUR was significantly positively correlated with the abundance of neutrophils. Significant higher abundance of PLAUR in DM-ILD patients than healthy controls was validated by RT-qPCR. In conclusion, we identified PLAUR as an important player in regulating DM-ILD by neutrophil-associated immune response. These findings enrich our understanding, which may benefit DM-ILD patients.
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spelling pubmed-86854572021-12-21 Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease Chen, Juan Zhang, Ruixian Xie, Min Luan, Chunyan Li, Xiaolan Front Genet Genetics Dermatomyositis (DM), an inflammatory disorder, is often associated with interstitial lung disease (ILD). However, the underlying mechanism remains unclear. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of differentially expressed genes (DEGs) in patients with dermatomyositis-associated interstitial lung disease (DM-ILD) and healthy controls. A total of 2,018 DEGs were identified between DM-ILD and healthy blood samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that DEGs were mainly involved in immune- and inflammatory-related biological processes and pathways. Disease ontology (DO) enrichment analysis identified 35 candidate key genes involved in both skin and lung diseases. Meanwhile, a total of 886 differentially expressed alternative splicing (AS) events were found between DM-ILD and healthy blood samples. After overlapping DEGs with differential AS genes, the plasminogen activator and urokinase receptor (PLAUR) involved in immune-related biological processes and complement and coagulation cascades was screened and identified as the most important gene associated with DM-ILD. The protein–protein interaction (PPI) network revealed that PLAUR had interactions with multiple candidate key genes. Moreover, we observed that there were significantly more neutrophils and less naive B cells in DM-ILD samples than in healthy samples. And the expression of PLAUR was significantly positively correlated with the abundance of neutrophils. Significant higher abundance of PLAUR in DM-ILD patients than healthy controls was validated by RT-qPCR. In conclusion, we identified PLAUR as an important player in regulating DM-ILD by neutrophil-associated immune response. These findings enrich our understanding, which may benefit DM-ILD patients. Frontiers Media S.A. 2021-12-06 /pmc/articles/PMC8685457/ /pubmed/34938325 http://dx.doi.org/10.3389/fgene.2021.784215 Text en Copyright © 2021 Chen, Zhang, Xie, Luan and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Chen, Juan
Zhang, Ruixian
Xie, Min
Luan, Chunyan
Li, Xiaolan
Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease
title Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease
title_full Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease
title_fullStr Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease
title_full_unstemmed Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease
title_short Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease
title_sort transcriptome sequencing identifies plaur as an important player in patients with dermatomyositis-associated interstitial lung disease
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685457/
https://www.ncbi.nlm.nih.gov/pubmed/34938325
http://dx.doi.org/10.3389/fgene.2021.784215
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