Background Mesangial proliferation is a key pathologic feature of diagnosis and also a risk factor for progression in immunoglobulin A nephropathy (IgAN). We aimed to investigate the gene expression profiles of IgAN glomerulus according to the presence of mesangial proliferation. Methods We performed spatial-specific transcriptomic profiling for formalin-fixed-paraffin-embedded kidney biopsy tissues using the GeoMX Digital Spatial Profiler. A total of 3 glomeruli with direct pathologic classification for each case were profiled, including 12 cases (4 M1-IgAN, 4 M0-IgAN, and 4 donor controls). The differentially expressed genes (DEGs) were analyzed between the groups with gene ontology (GO) term annotation. Results In the result which successfully enriched glom-specific genes, M1-IgAN were distinctively separated from controls (77 upregulated and 55 downregulated DEGs), while certain 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). The upregulated DEG that was consistent in M1-IgAN and M0-IgAN cases was TCF21 which is known as early podocyte injury marker while the DEGs uniformly downregulated in IgAN cases included ATF3, EGR1, DUSP1, FOS, JUNB, KLF2, KLF4, NR4A1, RHOB, and ZFP36. Glomeruli from M1-IgAN cases were significantly enriched for cell surface/adhesion molecules and the gene expressions that consist vascular development or extracellular matrix. Conclusion We found certain transcriptomic differences according to the histologic changes in IgAN which was present even in the early stage of the disease. Spatial transcriptomic analysis may contribute to dissecting structure-specific pathogenesis and molecular changes in IgAN.

The authors have declared no competing interest.

The biospecimens for this study were provided by the Seoul National University Hospital Human Biobank, a member of the Korea Biobank Network, which is supported by the Ministry of Health and Welfare. This research was supported by a grant from National Research Fund of Republic of Korea (2022R1A2C2011190). This research was supported by a grant of the MD/Phd/Medical Scientist Training Program through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea. This study was supported by the 2022 Young Investigator Research Grant from the KOREAN NEPHROLOGY RESEARCH FOUNDATION.

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This study was approved by the Institutional Reviewer Boards of Seoul National University Hospital (IRB No. H-2205-104-1325). All biospecimens and clinical data were collected after appropriate informed consent by the patients. This study was performed in accordance to the declaration of Helsinki.

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