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Mechanistic Investigation of Five Small-Molecule Inhibitors in the Treatment of Pemphigus Vulgaris via RNA-Seq Analysis

GSE285009 Homo sapiens Expression profiling by high throughput sequencing 34 samples 2025/02/10 GPL24676
Summary
Pemphigus vulgaris (PV) is an autoimmune disorder characterized by autoantibodies (AAbs) against Desmoglein 1 (DSG1) and Desmoglein 3 (DSG3) on keratinocytes, resulting in compromised cell-cell adhesion and epidermal blistering. To explore potential therapeutic targets, five small-molecule inhibitors, A66 (PI3Kα inhibitor), BIRB796 (p38 MAPK inhibitor), GW441756 (TrkA inhibitor), Selumetinib (MEK1 inhibitor), and Vandetanib (VEGFR2 inhibitor) were selected through a screen identifying compounds that reduce split formation in a human skin organ culture (HSOC) model. Each inhibitor exhibits distinct transcriptomic profiles that contribute to gene expression modulation, yet all share a common downregulation of chemokine signaling pathways associated with split formation. These inhibitors, capable of mitigating skin blistering in PV, present potential as therapeutic agents for this challenging autoimmune condition.
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