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Abstract: TH-PO427

Bowman Capsular Laser Irradiation Induces Parietal Migration of Renin Cells in Longitudinal Three-Dimensional Intravital Microscopy

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 600 Development, Stem Cells, and Regenerative Medicine

Authors

  • Arndt, Patrick, Experimental Nephrology, Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
  • Sradnick, Jan, Experimental Nephrology, Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
  • Azizolli, Shila, Experimental Nephrology, Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
  • Halder, Sagor, Experimental Nephrology, Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
  • Todorov, Vladimir T., Experimental Nephrology, Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
  • Hugo, Christian, Experimental Nephrology, Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
Background

Renin cells reside in the juxtaglomerular apparatus and serve as progenitors capable of migrating into the glomerulus following injury. These glomerular repair processes involve an individual intraglomerular-juxtaglomerular feedback mechanism. Using longitudinal intravital microscopy and a laser injury model to induce localized damage in individual glomeruli allows for controlled observation of repair processes. Laser irradiation of the Bowman capsule provides further insights into the migration processes of renin cells modeling glomerular damage and tubulointerstitial injures similar to Bowman capsule rupture in ANCA-associated GN.

Methods

Renin tdTomato reporter mice were subjected to doxycycline treatment for 3 weeks. Intravital microscopy was performed through an implanted body window using an upright 2-photon microscope for 3 hours on day 1 and after 96 hours. Laser injury was induced by focusing 100% laser power for 5 to 20 seconds at 12x to 48x zoom on one Z-plane. 3D processing was performed with Bitplane Imaris 10.1. Tdtomato+ cells and parietal epithelial cells were identified through immunohistochemistry in PFA-fixed kidney cryosections.

Results

The targeted use of a laser injury model induced reproducible capsular and trans-capsule injuries in murine nephrons. In 39 nephrons with capsular injury, renin cells migrated parietally in 36% and intraglomerularly towards the laser irradiated area in 41% of all cases. In 8 nephrons (20%), the renin cells migrated both parietally and intraglomerularly. No migration occurred in 23% of the nephrons with capsular injury. Migrating renin cells were able to connect to capsular injuries opposite from the juxtaglomerular apparatus with a tdTomato signal chain keeping contact to their niche of origin.

Conclusion

Longitudinal intravital microscopy combined with a capsular-targeted laser injury model and 3D image analysis in transgenic mice revealed an additional pathway for renin cell migration. Besides direct migration towards intraglomerular injuries, renin cells are also capable of parietal migration towards capsular damage linking them to glomerular-tubulointerstitial regeneration. Further research may investigate the juxtaglomerular feedback system of renin cell recruitment/migration, transdifferentiation and regenerative site-specific responses.

Funding

  • Government Support – Non-U.S.