Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents
Abstract Background IgA nephropathy (IgAN) is a kidney disease recognized by the presence of IgA antibody depositions in kidneys. The underlying mechanisms of this complicated disease are remained to be explored and still, there is an urgent need for the discovery of noninvasive biomarkers for its d...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-04-01
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| Series: | BMC Nephrology |
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| Online Access: | https://doi.org/10.1186/s12882-021-02356-4 |
| _version_ | 1818961023805161472 |
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| author | Alieh Gholaminejad Yousof Gheisari Sedigheh Jalali Amir Roointan |
| author_facet | Alieh Gholaminejad Yousof Gheisari Sedigheh Jalali Amir Roointan |
| author_sort | Alieh Gholaminejad |
| collection | DOAJ |
| description | Abstract Background IgA nephropathy (IgAN) is a kidney disease recognized by the presence of IgA antibody depositions in kidneys. The underlying mechanisms of this complicated disease are remained to be explored and still, there is an urgent need for the discovery of noninvasive biomarkers for its diagnosis. In this investigation, an integrative approach was applied to mRNA and miRNA expression profiles in PBMCs to discover a gene signature and novel potential targets/biomarkers in IgAN. Methods Datasets were selected from gene expression omnibus database. After quality control checking, two datasets were analyzed by Limma to identify differentially expressed genes/miRNAs (DEGs and DEmiRs). Following identification of DEmiR-target genes and data integration, intersecting mRNAs were subjected to different bioinformatic analyses. The intersecting mRNAs, DEmiRs, related transcription factors (from TRRUST database), and long-non coding RNAs (from LncTarD database) were used for the construction of a multilayer regulatory network via Cytoscape. Result “GSE25590” (miRNA) and “GSE73953” (mRNA) datasets were analyzed and after integration, 628 intersecting mRNAs were identified. The mRNAs were mainly associated with “Innate immune system”, “Apoptosis”, as well as “NGF signaling” pathways. A multilayer regulatory network was constructed and several hub-DEGs (Tp53, STAT3, Jun, etc.), DEmiRs (miR-124, let-7b, etc.), TFs (NF-kB, etc.), and lncRNAs (HOTAIR, etc.) were introduced as potential factors in the pathogenesis of IgAN. Conclusion Integration of two different expression datasets and construction of a multilayer regulatory network not only provided a deeper insight into the pathogenesis of IgAN, but also introduced several key molecules as potential therapeutic target/non-invasive biomarkers. |
| first_indexed | 2024-12-20T12:06:50Z |
| format | Article |
| id | doaj.art-92516c7e51c242d3aaae844f562793ab |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-12-20T12:06:50Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-92516c7e51c242d3aaae844f562793ab2022-12-21T19:41:22ZengBMCBMC Nephrology1471-23692021-04-0122111010.1186/s12882-021-02356-4Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agentsAlieh Gholaminejad0Yousof Gheisari1Sedigheh Jalali2Amir Roointan3Regenerative medicine research center, Isfahan University of Medical SciencesRegenerative medicine research center, Isfahan University of Medical SciencesDepartment of Pediatrics, The University of MelbourneRegenerative medicine research center, Isfahan University of Medical SciencesAbstract Background IgA nephropathy (IgAN) is a kidney disease recognized by the presence of IgA antibody depositions in kidneys. The underlying mechanisms of this complicated disease are remained to be explored and still, there is an urgent need for the discovery of noninvasive biomarkers for its diagnosis. In this investigation, an integrative approach was applied to mRNA and miRNA expression profiles in PBMCs to discover a gene signature and novel potential targets/biomarkers in IgAN. Methods Datasets were selected from gene expression omnibus database. After quality control checking, two datasets were analyzed by Limma to identify differentially expressed genes/miRNAs (DEGs and DEmiRs). Following identification of DEmiR-target genes and data integration, intersecting mRNAs were subjected to different bioinformatic analyses. The intersecting mRNAs, DEmiRs, related transcription factors (from TRRUST database), and long-non coding RNAs (from LncTarD database) were used for the construction of a multilayer regulatory network via Cytoscape. Result “GSE25590” (miRNA) and “GSE73953” (mRNA) datasets were analyzed and after integration, 628 intersecting mRNAs were identified. The mRNAs were mainly associated with “Innate immune system”, “Apoptosis”, as well as “NGF signaling” pathways. A multilayer regulatory network was constructed and several hub-DEGs (Tp53, STAT3, Jun, etc.), DEmiRs (miR-124, let-7b, etc.), TFs (NF-kB, etc.), and lncRNAs (HOTAIR, etc.) were introduced as potential factors in the pathogenesis of IgAN. Conclusion Integration of two different expression datasets and construction of a multilayer regulatory network not only provided a deeper insight into the pathogenesis of IgAN, but also introduced several key molecules as potential therapeutic target/non-invasive biomarkers.https://doi.org/10.1186/s12882-021-02356-4IgA nephropathyComputational biologyGene expressionGene regulatory networkBiomarkers |
| spellingShingle | Alieh Gholaminejad Yousof Gheisari Sedigheh Jalali Amir Roointan Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents BMC Nephrology IgA nephropathy Computational biology Gene expression Gene regulatory network Biomarkers |
| title | Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents |
| title_full | Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents |
| title_fullStr | Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents |
| title_full_unstemmed | Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents |
| title_short | Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents |
| title_sort | comprehensive analysis of iga nephropathy expression profiles identification of potential biomarkers and therapeutic agents |
| topic | IgA nephropathy Computational biology Gene expression Gene regulatory network Biomarkers |
| url | https://doi.org/10.1186/s12882-021-02356-4 |
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