Transmembrane signaling molecules play a key role in the pathogenesis of IgA nephropathy: a weighted gene co-expression network analysis study

Abstract Background Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulonephritis and a serious health concern worldwide; though still the underlying molecular mechanisms of IgAN are yet to be known and there is no efficient treatment for this disease. The main goal of thi...

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Autores principales: Alieh Gholaminejad, Amir Roointan, Yousof Gheisari
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Publicado: BMC 2021
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spelling oai:doaj.org-article:1a156e4024c9415ca4f9c8cdc93aee4a2021-12-05T12:05:47ZTransmembrane signaling molecules play a key role in the pathogenesis of IgA nephropathy: a weighted gene co-expression network analysis study10.1186/s12865-021-00468-y1471-2172https://doaj.org/article/1a156e4024c9415ca4f9c8cdc93aee4a2021-12-01T00:00:00Zhttps://doi.org/10.1186/s12865-021-00468-yhttps://doaj.org/toc/1471-2172Abstract Background Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulonephritis and a serious health concern worldwide; though still the underlying molecular mechanisms of IgAN are yet to be known and there is no efficient treatment for this disease. The main goal of this study was to explore the IgAN underlying pathogenic pathways, plus identifying the disease correlated modules and genes using the weighted gene co-expression network analysis (WGCNA) algorithm. Results GSE104948 dataset (the expression data from glomerular tissue of IgAN patients) was analyzed and the identified differentially expressed genes (DEGs) were introduced to the WGCNA algorithm for building co-expression modules. Genes were classified into six co-expression modules. Genes of the disease’s most correlated module were mainly enriched in the immune system, cell–cell communication and transmembrane cell signaling pathways. The PPI network was constructed by genes in all the modules and after hub-gene identification and validation steps, 11 genes, mostly transmembrane proteins (CD44, TLR1, TLR2, GNG11, CSF1R, TYROBP, ITGB2, PECAM1), as well as DNMT1, CYBB and PSMB9 were identified as potentially key players in the pathogenesis of IgAN. In the constructed regulatory network, hsa-miR-129-2-3p, hsa-miR-34a-5p and hsa-miR-27a-3p, as well as STAT3 were spotted as top molecules orchestrating the regulation of the hub genes. Conclusions The excavated hub genes from the hearts of co-expressed modules and the PPI network were mostly transmembrane signaling molecules. These genes and their upstream regulators could deepen our understanding of IgAN and be considered as potential targets for hindering its progression.Alieh GholaminejadAmir RoointanYousof GheisariBMCarticleIgA nephropathyWeighted gene co-expression networkDifferentially expressed genesHub genesDrug targetImmunologic diseases. AllergyRC581-607ENBMC Immunology, Vol 22, Iss 1, Pp 1-17 (2021)
institution DOAJ
collection DOAJ
language EN
topic IgA nephropathy
Weighted gene co-expression network
Differentially expressed genes
Hub genes
Drug target
Immunologic diseases. Allergy
RC581-607
spellingShingle IgA nephropathy
Weighted gene co-expression network
Differentially expressed genes
Hub genes
Drug target
Immunologic diseases. Allergy
RC581-607
Alieh Gholaminejad
Amir Roointan
Yousof Gheisari
Transmembrane signaling molecules play a key role in the pathogenesis of IgA nephropathy: a weighted gene co-expression network analysis study
description Abstract Background Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulonephritis and a serious health concern worldwide; though still the underlying molecular mechanisms of IgAN are yet to be known and there is no efficient treatment for this disease. The main goal of this study was to explore the IgAN underlying pathogenic pathways, plus identifying the disease correlated modules and genes using the weighted gene co-expression network analysis (WGCNA) algorithm. Results GSE104948 dataset (the expression data from glomerular tissue of IgAN patients) was analyzed and the identified differentially expressed genes (DEGs) were introduced to the WGCNA algorithm for building co-expression modules. Genes were classified into six co-expression modules. Genes of the disease’s most correlated module were mainly enriched in the immune system, cell–cell communication and transmembrane cell signaling pathways. The PPI network was constructed by genes in all the modules and after hub-gene identification and validation steps, 11 genes, mostly transmembrane proteins (CD44, TLR1, TLR2, GNG11, CSF1R, TYROBP, ITGB2, PECAM1), as well as DNMT1, CYBB and PSMB9 were identified as potentially key players in the pathogenesis of IgAN. In the constructed regulatory network, hsa-miR-129-2-3p, hsa-miR-34a-5p and hsa-miR-27a-3p, as well as STAT3 were spotted as top molecules orchestrating the regulation of the hub genes. Conclusions The excavated hub genes from the hearts of co-expressed modules and the PPI network were mostly transmembrane signaling molecules. These genes and their upstream regulators could deepen our understanding of IgAN and be considered as potential targets for hindering its progression.
format article
author Alieh Gholaminejad
Amir Roointan
Yousof Gheisari
author_facet Alieh Gholaminejad
Amir Roointan
Yousof Gheisari
author_sort Alieh Gholaminejad
title Transmembrane signaling molecules play a key role in the pathogenesis of IgA nephropathy: a weighted gene co-expression network analysis study
title_short Transmembrane signaling molecules play a key role in the pathogenesis of IgA nephropathy: a weighted gene co-expression network analysis study
title_full Transmembrane signaling molecules play a key role in the pathogenesis of IgA nephropathy: a weighted gene co-expression network analysis study
title_fullStr Transmembrane signaling molecules play a key role in the pathogenesis of IgA nephropathy: a weighted gene co-expression network analysis study
title_full_unstemmed Transmembrane signaling molecules play a key role in the pathogenesis of IgA nephropathy: a weighted gene co-expression network analysis study
title_sort transmembrane signaling molecules play a key role in the pathogenesis of iga nephropathy: a weighted gene co-expression network analysis study
publisher BMC
publishDate 2021
url https://doaj.org/article/1a156e4024c9415ca4f9c8cdc93aee4a
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AT amirroointan transmembranesignalingmoleculesplayakeyroleinthepathogenesisofiganephropathyaweightedgenecoexpressionnetworkanalysisstudy
AT yousofgheisari transmembranesignalingmoleculesplayakeyroleinthepathogenesisofiganephropathyaweightedgenecoexpressionnetworkanalysisstudy
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