ArticleFrontiers in nephrology2026
Spatial transcriptomic analysis of kidney biopsies identifies activation of complement and SPP1 networks in
Article in Frontiers in nephrology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Methods: To dissect the complex underlying immunopathology, we analyzed formalin-fixed paraffin-embedded kidney biopsy tissues from three patients with SAGN and one normal control kidney (NCK) using single-cell spatial transcriptomics (analyzing a total of 3,993 cell-specific transcriptomes). The SAGN biopsies showed diffuse endocapillary hypercellularity with focal crescents. Following annotation of various cell types, we constructed cell communication networks using CellChat to identify ligand-receptor interactions in normal and SAGN kidneys. Results: Secreted phosphoprotein 1 (SPP1/osteopontin) emerged as the most enriched signaling network in SAGN with markedly increased autocrine and paracrine SPP1-CD44 activity among tubular segments and parietal epithelial cells (PECs). In contrast, SPP1-integrin signaling was mainly observed in healthy control kidneys. Consistent with previous reports, complement pathway activation was detected exclusively in diseased kidneys, with PECs as principal signal receivers, suggesting the potential role in crescent formation. Transcripts for C2, C3, CD55, Factor B, and Factor D showed significant upregulation in SAGN. In contrast, vascular endothelial growth factor (VEGF), angiopoietin-like proteins (ANG PTL), and progranulin/granulin networks exhibited decreased communication probabilities in SAGN versus NCK, suggesting the suppression of protective angiogenic and anti-inflammatory signaling. Immunofluorescence staining for SPP1 showed increased staining in renal tubular segments in SAGN biopsies, supporting our transcriptomic data. Conclusion: SPP1 and complement pathways appear to drive pro-inflammatory responses, while protective VEGF signaling is compromised, providing potential therapeutic targets for this disease.
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