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Kidney Week

Abstract: TH-PO405

Impact of Renin on the Migration of Renin-Positive Cells in the Course of CKD

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 600 Development, Stem Cells, and Regenerative Medicine

Authors

  • Azizolli, Shila, Universitatsklinikum Carl Gustav Carus, Dresden, Sachsen, Germany
  • Halder, Sagor, Universitatsklinikum Carl Gustav Carus, Dresden, Sachsen, Germany
  • Schuster, Maria, Universitatsklinikum Carl Gustav Carus, Dresden, Sachsen, Germany
  • Gembardt, Florian, Universitatsklinikum Carl Gustav Carus, Dresden, Sachsen, Germany
  • Sradnick, Jan, Universitatsklinikum Carl Gustav Carus, Dresden, Sachsen, Germany
  • Panzer, Ulf, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
  • Hugo, Christian, Universitatsklinikum Carl Gustav Carus, Dresden, Sachsen, Germany
Background

Renin-positive juxtaglomerular cells (RPC) have been shown to serve as precursors for various glomerular cell types in models of acute kidney injury. Specifically, we have previously demonstrated their ability to migrate intraglomerularly and differentiate into mesangial cells upon losing their renin-positivity. However, the role of RPC and their mechanisms in chronic injury models remains unknown. Therefore, we aimed to evaluate the role of renin and RPC migration in the chronic disease model of anti-glomerular basement membrane (anti-GBM), using an inducible renin-knockout (RenKO) mouse line.

Methods

Inducible transgenic renin-reporter (WT) and RenKO 8-12 week mice were used. The injury model was initiated by an intraperitoneal (i.p) injection of TNF-α. Two hours later, anti-GBM serum was administered i.p. To examine the effects of the model, a uni-nephrectomy was performed on day 10 after serum injection, followed by the final biopsy on day 21. PAS staining was used to assess the renal damage. RPC migration was analyzed using immunofluorescence staining against tdTomato, a8-Integrin, and renin. The extent of RPC migration was determined by the glomerular tdTomato-positive areas.

Results

PAS staining of the samples from both WT and RenKO groups, revealed substantial glomerular injury upon anti-GBM model induction. The damage was marked by the emergence of tubular casts, high PAS-positivity, and crescent formation.
The immunofluorescence staining revealed significant differences between the groups in terms of RPC migration. At day 10, RPC migration was observed in 45% and 13% (p-value < 0.0001) of the overall glomeruli in WT and RenKO after anti-GBM induction, respectively. Additionally, at day 21 RPC migration was observed in 50% and 12% (p-value = 0.0002) of the overall glomeruli in WT and RenKO respectively.

Conclusion

In conclusion, we were able to demonstrate for the first time, RPC migration during a chronically progressive kidney injury model. Since renin depletion leads to significantly reduced migration, renin itself appears to be involved in this process. Next, a thorough analysis of the injury advancement between the groups, and a characterization of the transcriptomic landscape of the RPC under healthy and pathological conditions will provide further clarity on this mechanism.