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Abstract: PO1681

Primary Cilia in Podocyte Health and Disease

Session Information

Category: Glomerular Diseases

  • 1204 Podocyte Biology

Authors

  • Fitzsimons, Lindsey Avery, University of Maine at Orono, Graduate School of Biomedical Science & Engineering, Orono, Maine, United States
  • Button, Kara M., University of New England College of Osteopathic Medicine, Biddeford, Maine, United States
  • Cho, Jake Namjik, Maine Medical Center, Portland, Maine, United States
  • Akom, Michael C., Maine Medical Center, Portland, Maine, United States
  • Tucker, Kerry L., University of New England College of Osteopathic Medicine, Biddeford, Maine, United States
  • Korstanje, Ron, The Jackson Laboratory, Bar Harbor, Maine, United States
Background

Primary cilia are highly specialized elaborations of the plasma membrane that direct many of the signaling cascades critical for pre- and post-natal development and disease. While renal primary cilia are recognized as key genetic and cellular targets in polycystic kidney disease, the presence and function of primary cilia within the renal corpuscle and glomerulus have yet to be fully characterized. The purpose of our study was to perform a focused and quantifiable characterization of primary cilia of glomerular cell populations in health and disease.

Methods

Renal biopsy samples were obtained from patients with Minimal Change Disease (MCD; N=6), Focal Segmental Glomerular Sclerosis (FSGS; N=3), and control renal tissue (CON; N=4). Immunofluorescence analyses (IF) were used to quantify primary cilia number and length, as well as the expression of Sonic Hedgehog (SHH) protein, the ligand component of the Hedgehog signaling pathway and one measure of primary cilia function.

Results

Mean percent ciliation was significantly increased in MCD and FSGS when compared to CON. Analysis of individual glomerular primary cilia revealed increased ciliary length (μm) in both MCD and FSGS when compared to CON. Further analysis comparing primary cilia length in WT-1-positive nuclei (WT-1+; podocytes) also revealed a pronounced increase in cilia length in MCD and FSGS podocyte primary cilia versus CON. Despite increased length of primary cilia, glomerular SHH expression was significantly decreased in both MCD and FSGS when compared to CON. Glomerular diseases MCD and FSGS are therefore associated with an overall increase in podocyte primary cilia length and ciliation, an effect which corresponded to a decrease in SHH expression.

Conclusion

These data provide evidence in support of a role for primary cilia in glomerular disease pathogenesis. Ongoing and future research is needed to establish a mechanistic explanation for these changes observed in glomerular and podocyte cilia number and length. A more thorough understanding of the role(s) of primary cilia in glomerular cells, and specifically in podocytes, remains critical for to both our understanding of disease pathogenesis as well as for the pharmacologic treatment of glomerular chronic kidney disease.

Funding

  • Private Foundation Support