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Updated: Aug 26, 2026
A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
Renin Is Critical for Renin-Lineage Cell Plasticity, Migration, and Disease Outcome in Experimental Crescentic GN
Shila Azizolli1, Sagor Halder1, Anne Steglich1
1Department of Internal Medicine III, Division of Nephrology, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.
Key Points:
Renin deficiency in renin-lineage cells worsened crescentic GN and was associated with lower glomerular cell migration. Loss of renin altered immune-associated, metabolic, and migratory transcriptional programs in renin-lineage cells. Renin-lineage cell ablation reduced macrophage/leukocyte infiltration but had limited effects on overall disease severity.
Background:
The adult juxtaglomerular renin-lineage cell niche demonstrates cellular plasticity after injury, but its role in highly inflammatory crescentic GN remains unclear. While renin-angiotensin signaling promotes fibrosis and inflammation, the contribution of the renin-lineage cells and renin expression within these cells to crescentic GN has not been investigated.
Methods:
We used tdTomato lineage tracing to track renin-lineage cells in wild-type (WT) and renin-knockout (RenKO) mice after crescentic GN induction. Renin-lineage cell migration and glomerular injury were quantified histologically. Single-cell RNA sequencing was performed on isolated tdTomato-positive cells on days 10 and 21 after injury to characterize transcriptional programs. Disease progression was additionally examined in mice with diphtheria toxin A-mediated renin-lineage cell ablation.
Results:
Renin-lineage cells were detected within injured glomeruli during crescentic GN. Genetic renin deletion worsened disease outcomes, with RenKO mice developing increased albuminuria (by 3-fold), crescent formation (by 50%), and podocyte loss (by 15%) by day 21 compared with WT controls. Renin-deficient renin-lineage cells exhibited reduced glomerular migration and decreased colocalization with mesangial cell markers. Single-cell transcriptomic analysis revealed distinct transcriptional programs between WT and RenKO renin-lineage cells, with RenKO cells enriched for IFN-stimulated and reduced migration-associated pathways. Renin-lineage cell ablation reduced macrophage infiltration but did not alter disease severity.
Conclusions:
Renin expression influenced migration and injury-associated responses of renin-lineage cells during crescentic GN. Loss of renin was associated with a dysfunctional IFN-driven and antimigratory phenotype together with more severe glomerular injury, whereas renin-lineage cell ablation reduced macrophage infiltration but had limited effects on overall disease severity.
