ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO707

Podocytes Respond to Mechanical Forces to Spatially Orient Their Processes on Glomerular Capillaries

Session Information

Category: Glomerular Diseases

  • 1304 Glomerular Diseases: Podocyte Biology

Authors

  • Unnersjö-Jess, David, Uniklinik Koln, Koln, Germany
  • Ramdedovic, Amer, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Butt, Linus, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Plagmann, Ingo, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Höhne, Martin, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Blom, Hans, Kungliga Tekniska Hogskolan, Stockholm, Sweden
  • Hackl, Agnes, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Schermer, Bernhard, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Benzing, Thomas, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
Background

It has recently been proposed by our group that the main role of podocyte foot processes is to counteract forces resulting from filtration pressure in order to compress the basement membrane, thereby optimizing sieving properties. We here expand on these models by studying the role of spatial orientation of foot processes on glomerular capillaries.

Methods

We apply novel imaging protocols which allow for confocal in-situ 3D imaging of intact glomerular capillaries at a resolution sufficient to resolve foot processes. This allows for analyzing several thousands of podocyte processes and quantitatively determine their spatial orientation with regards to the capillary orientation.

Results

We report the novel finding that podocyte processes display a non-random distribution on glomerular capillaries, which is lost in different types of kidney disease. This finding suggests that the orientation of foot processes is important for the function of the filtration barrier. We further observe a more prominent orientation preference in elongated and more cylindrical capillary segments, where the difference between circumferential and longitudinal wall stress is highest. This strongly indicates that podocytes possess a machinery to regulate and maintain the spatial orientation of their processes based on the forces acting on them.

Conclusion

We consider the various forces that foot processes are exposed to and conclude that the observed orientation of foot processes in parallel with the orientation axis of capillaries is likely to ensure that slit diaphragm molecules (e.g. nephrin, NEPH1) are preferably aligned in parallel with the axis of highest wall stress. This adds further evidence to the theory that foot processes and the slit diaphragm act to mechanically counteract lateral wall stress, but also possesses a mechanosensory machinery for maintaining orientation on capillaries.

New imaging protocols allow for determining the orientation of foot processes based on nephrin staining (green).

Funding

  • Private Foundation Support