Comprehensive Transcriptomic Analysis with Deconvolution and In Vivo Experiments Reveal the Role of the NLRP3 Inflammasome in Crescentic Glomerulonephritis.
- 1Department of Nephrology, Showa Medical University Graduate School of Medicine, Tokyo, Japan.
- 2Department of Nephrology, Showa Medical University Graduate School of Medicine, Tokyo, Japan. [email protected].
- 3Department of Microbiology and Immunology, Showa Medical University Graduate School of Medicine, Tokyo, Japan.
Abstract
Crescentic glomerulonephritis (CrGN) is a severe histological phenotype of immune mediated kidney disease. Although NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation has been implicated in CrGN, its involvement in human glomerular components remains unclear. We reanalyzed publicly available glomerular microarray data from patients with glomerular diseases. We also integrated the mixture matrix from this microarray data with the signature matrix from single nucleus RNA sequencing data using BayesPrism-based deconvolution. NLRP3 inflammasome pathway activity was assessed by gene set variation analysis and validated by immunostaining for NLRP3 using human kidney biopsy specimens. Furthermore, we conducted in vivo experiments using a rat CrGN model treated with shikonin known as an NLRP3 inflammasome inhibitor. NLRP3 inflammasome pathway activation was most prominent in anti-neutrophil cytoplasmic antibody-associated vasculitis. Deconvolution analysis demonstrated increased NLRP3 inflammasome pathway activity across podocytes, parietal epithelial cells (PECs), endothelial cells, and mesangial cells. Human kidney biopsy specimens confirmed increased NLRP3 expression in podocytes and PECs. In the rat CrGN model, shikonin reduced proteinuria, serum creatinine, crescent formation, and podocyte injury, accompanied by decreased expression of NLRP3 inflammasome related genes, and reduced NLRP3 protein expression in podocytes and parietal epithelial cells. NLRP3 inflammasome activation in glomerular resident cells may contribute to AAV-associated CrGN pathogenesis, and pharmacological modulation of this pathway could represent a therapeutic strategy for CrGN.
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BibTeX
@article{kobayashi2026comprehensive,
title = {{Comprehensive Transcriptomic Analysis with Deconvolution and In Vivo Experiments Reveal the Role of the NLRP3 Inflammasome in Crescentic Glomerulonephritis.}},
author = {Kazuki Kobayashi and Taihei Suzuki and Yuki Kajio and Masataka Ueda and Mayuko Orikasa and Shiho Tamura and Nobuhiro Kanazawa and Masayuki Iyoda and Hirokazu Honda},
journal = {Inflammation},
year = {2026},
month = jul,
doi = {10.1007/s10753-026-02571-x},
url = {https://europepmc.org/article/MED/42967957},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Comprehensive Transcriptomic Analysis with Deconvolution and In Vivo Experiments Reveal the Role of the NLRP3 Inflammasome in Crescentic Glomerulonephritis.
AU - Kazuki Kobayashi
AU - Taihei Suzuki
AU - Yuki Kajio
AU - Masataka Ueda
AU - Mayuko Orikasa
AU - Shiho Tamura
AU - Nobuhiro Kanazawa
AU - Masayuki Iyoda
AU - Hirokazu Honda
PY - 2026
DA - 2026/07/30
JO - Inflammation
DO - 10.1007/s10753-026-02571-x
UR - https://europepmc.org/article/MED/42967957
AB - Crescentic glomerulonephritis (CrGN) is a severe histological phenotype of immune mediated kidney disease. Although NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation has been implicated in CrGN, its involvement in human glomerular components remains unclear. We reanalyzed publicly available glomerular microarray data from patients with glomerular diseases. We also integrated the mixture matrix from this microarray data with the signature matrix from single nucleus RNA sequencing data using BayesPrism-based deconvolution. NLRP3 inflammasome pathway activity was assessed by gene set variation analysis and validated by immunostaining for NLRP3 using human kidney biopsy specimens. Furthermore, we conducted in vivo experiments using a rat CrGN model treated with shikonin known as an NLRP3 inflammasome inhibitor. NLRP3 inflammasome pathway activation was most prominent in anti-neutrophil cytoplasmic antibody-associated vasculitis. Deconvolution analysis demonstrated increased NLRP3 inflammasome pathway activity across podocytes, parietal epithelial cells (PECs), endothelial cells, and mesangial cells. Human kidney biopsy specimens confirmed increased NLRP3 expression in podocytes and PECs. In the rat CrGN model, shikonin reduced proteinuria, serum creatinine, crescent formation, and podocyte injury, accompanied by decreased expression of NLRP3 inflammasome related genes, and reduced NLRP3 protein expression in podocytes and parietal epithelial cells. NLRP3 inflammasome activation in glomerular resident cells may contribute to AAV-associated CrGN pathogenesis, and pharmacological modulation of this pathway could represent a therapeutic strategy for CrGN.
SN - 0360-3997
SN - 1573-2576
ER -