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

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...

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Autores principales: Gholaminejad, Alieh, Roointan, Amir, Gheisari, Yousof
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642929/
https://www.ncbi.nlm.nih.gov/pubmed/34861820
http://dx.doi.org/10.1186/s12865-021-00468-y
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author Gholaminejad, Alieh
Roointan, Amir
Gheisari, Yousof
author_facet Gholaminejad, Alieh
Roointan, Amir
Gheisari, Yousof
author_sort Gholaminejad, Alieh
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12865-021-00468-y.
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spelling pubmed-86429292021-12-06 Transmembrane signaling molecules play a key role in the pathogenesis of IgA nephropathy: a weighted gene co-expression network analysis study Gholaminejad, Alieh Roointan, Amir Gheisari, Yousof BMC Immunol Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12865-021-00468-y. BioMed Central 2021-12-03 /pmc/articles/PMC8642929/ /pubmed/34861820 http://dx.doi.org/10.1186/s12865-021-00468-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Gholaminejad, Alieh
Roointan, Amir
Gheisari, Yousof
Transmembrane signaling molecules play a key role in the pathogenesis of IgA nephropathy: a weighted gene co-expression network analysis study
title 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_short 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642929/
https://www.ncbi.nlm.nih.gov/pubmed/34861820
http://dx.doi.org/10.1186/s12865-021-00468-y
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