Mesangial proliferation is a diagnostic feature and a prognostic predictor of immunoglobulin A nephropathy (IgAN). We aimed to investigate the gene expression profiles of IgAN glomerulus according to the presence of mesangial proliferation. We performed spatial-specific transcriptomic profiling on kidney biopsy tissues using the GeoMx Digital Spatial Profiler. Twelve cases with three glomeruli for each case were profiled using direct pathologic classification (4 M1-IgAN, 4 M0-IgAN, and 4 donor controls). The results of enriched glom-specific genes demonstrated that M1-IgAN could be distinguished from controls (77 upregulated and 55 downregulated DEGs), while some DEGs were identified between M1-IgAN and M0-IgAN cases (24 upregulated and 8 downregulated DEGs) or between M0 and controls (1 upregulated and 16 downregulated DEGs). TCF21, an early podocyte damage marker, was the only differentially expressed gene (DEG) consistently upregulated in both M1-IgAN and M0-IgAN patients, whereas ATF3, EGR1, DUSP1, FOS, JUNB, KLF2, NR4A1, RHOB, and ZFP36 were consistently downregulated in IgAN cases. Glomeruli from M1-IgAN cases were significantly enriched for cell surface/adhesion molecules and gene expressions associated with vascular development or the extracellular matrix. Spatial transcriptomic analysis may contribute to dissecting structure-specific pathophysiology and molecular changes in IgAN.

系膜增生是免疫球蛋白 A 肾病 （IgAN） 的诊断特征和预后预测因子。我们旨在根据系膜增殖的存在来研究 IgAN 肾小球的基因表达谱。我们使用 GeoMx Digital Spatial Profiler 对肾活检组织进行了空间特异性转录组分析。使用直接病理分类 （4 例 M1-IgAN、4 例 M0-IgAN 和 4 例供体对照） 对 12 例病例进行剖析，每例有 3 个肾小球。富集的 glom 特异性基因结果表明，M1-IgAN 可以与对照区分开来 （77 个上调和 55 个下调的 DEGs），而在 M1-IgAN 和 M0-IgAN 病例之间 （24 个上调和 8 个下调 DEGs） 或 M0 和对照之间 （1 个上调和 16 个 DEGs下调）。TCF21 是一种早期足细胞损伤标志物，是唯一在 M1-IgAN 和 M0-IgAN 患者中持续上调的差异表达基因 （DEG），而 ATF3 、 EGR1 、 DUSP1 、 FOS 、 JUNB 、 KLF2 、 NR4A1 、 RHOB 和 ZFP36 在 IgAN 病例中持续下调。来自 M1-IgAN 病例的肾小球显著富集了细胞表面/粘附分子和与血管发育或细胞外基质相关的基因表达。空间转录组学分析可能有助于剖析 IgAN 的结构特异性病理生理学和分子变化。