23 DOI: https://doi.org/10.1016/j.jgeb.2025.100513 English eng Wang, YiRui Contributor <div id="as005" style="margin: 0px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="st010" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Introduction</h3><div class="u-margin-s-bottom" id="sp0005" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;">Several studies identified <a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/heredity" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">genetic factors</a><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"> and key <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/signal-transduction" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">cellular signaling</a> associated with developing </span><a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/immunoglobulin-a-nephropathy" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">immunoglobulin A nephropathy</a><span style="margin: 0px; padding: 0px;"> (IgAN). However, there is still a lack of understanding regarding the relationship between hub-transcription factors (TFs) encoding genes and changes in <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/immunogenicity" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">immunogenic activity</a><span style="margin: 0px; padding: 0px;">. Our objective was to identify hub-TF encoding genes associated with <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/immune-cell-infiltration" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">immune cell infiltrations</a>, immunogenic pathway activity, and potential drug candidates in IgAN through bioinformatics techniques.</span></span></span></div></div><div id="as010" style="margin: 0px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="st015" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Methods</h3><div class="u-margin-s-bottom" id="sp0010" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;">We utilized GSE104948, GSE93798, GSE115857, GSE37460, and GSE35487 to identify key significant DEGs and validation in IgAN relative to the control. Next, we employed various bioinformatics approaches to investigate the key genes and their relationship with immunity in IgAN. Finally, we identitified enriched drugs and elcudate their <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/molecular-interaction" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">molecular interactions</a><span style="margin: 0px; padding: 0px;"> with TFs via <a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/molecular-docking" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">molecular docking</a> approaches.</span></div></div><div id="as015" style="margin: 0px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="st020" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Results</h3><div class="u-margin-s-bottom" id="sp0015" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;"><span style="margin: 0px; padding: 0px;">We identified 1,123 differentially expressed genes (DEGs) between IgAN and control samples, comprising 342 upregulated genes and 780 downregulated genes. The upregulated genes are linked to immune-related <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/biological-phenomena-and-functions-concerning-the-entire-organism" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">biological processes</a> and KEGG pathways, while the downregulated genes are associated with metabolic processes. Five significant clusters were identified, enriched in several KEGG pathways. We explored 26 hub-TF encoding genes, including </span><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"><a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/transcription-factor-gata-2" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">GATA2</a></span><em style="margin: 0px; padding: 0px;">, </em></span><span style="margin: 0px; padding: 0px;"><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/hdac1" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">HDAC1</a></span><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"><em style="margin: 0px; padding: 0px;">, TSC22D3, </em><em style="margin: 0px; padding: 0px;"><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/sox9" title="Learn more about SOX9 from ScienceDirect's AI-generated Topic Pages" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">SOX9</a></em><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"><em style="margin: 0px; padding: 0px;">, RARA, RORA, </em><em style="margin: 0px; padding: 0px;"><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/klf5" title="Learn more about KLF5 from ScienceDirect's AI-generated Topic Pages" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">KLF5</a></em><em style="margin: 0px; padding: 0px;">, </em></span><em style="margin: 0px; padding: 0px;"><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/kmt2a" title="Learn more about KMT2A from ScienceDirect's AI-generated Topic Pages" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">KMT2A</a></em><em style="margin: 0px; padding: 0px;">, </em></span></span><span style="margin: 0px; padding: 0px;"><a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/fosb" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">FOSB</a></span><em style="margin: 0px; padding: 0px;">,</em></span></span> and <span style="margin: 0px; padding: 0px;"><em style="margin: 0px; padding: 0px;"><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fosl1" title="Learn more about FOSL1 from ScienceDirect's AI-generated Topic Pages" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">FOSL1</a></em></span><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;">, which were consistently dysregulated in IgAN patients. Immunogenic analysis revealed increased levels of <a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/th1-cell" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">Th1 cells</a>, </span><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/plasmacytoid-dendritic-cell" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">pDCs</a><span style="margin: 0px; padding: 0px;">, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/monocyte" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">monocytes</a><span style="margin: 0px; padding: 0px;">, <a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/m2-macrophages" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">M2 macrophages</a><span style="margin: 0px; padding: 0px;">, fibroblasts, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/endothelial-cell" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">endothelial cells</a>, and activated dendritic cells in IgAN. The activity of various immunological pathways was also elevated. The expression of hub-TFs like </span></span></span></span><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"><span style="margin: 0px; padding: 0px;"><a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/transcription-factor-gata-2" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">GATA2</a></span><em style="margin: 0px; padding: 0px;">, </em></span><em style="margin: 0px; padding: 0px;"><a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/histone-deacetylase-1" title="Learn more about HDAC1 from ScienceDirect's AI-generated Topic Pages" class="topic-link" style="margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">HDAC1</a></em><em style="margin: 0px; padding: 0px;">, TSC22D3, SOX9, RARA, RORA, KLF5, KMT2A, FOSB,</em></span> and <em style="margin: 0px; padding: 0px;">FOSL1</em> correlated with immune signatures and pathways in IgAN. Additionally, these hub-TFs were linked to diagnostic efficacy and drug interactions. Molecular docking identified key drug candidates for inhibiting HDAC1 and modulating RARA, suggesting their potential for IgAN treatment.</div></div><div id="as020" style="margin: 0px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="st025" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Conclusions</h3><div class="u-margin-s-bottom" id="sp0020" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;">We identified key hub-TFs and their association with immune infiltration and immune pathways linked to IgAN initiation and progression. These findings provide important insights into the immunological mechanisms driving IgAN and propose potential treatment approaches. Molecular docking further revealed key drug candidates for inhibiting and modulating these targets, highlighting their therapeutic potential for IgAN.</div></div> Elsevier September 2025 pdf Journal of Genetic Engineering and Biotechnology Integrative bioinformatics analysis unveils hub transcription factors and their interacting drugs in immunoglobulin A nephropathy: Implications for pathogenesis and treatments mixed material Elsevier