Abstract: FR-PO731
Vincristine Treatment Produces a Milieu Which Reverses Podocyte Damage in Focal Segmental Glomerulosclerosis
Session Information
- Glomerular Diseases: Podocyte Biology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1304 Glomerular Diseases: Podocyte Biology
Authors
- Mason, William John, University College London Institute of Child Health, London, London, United Kingdom
- Chandler, Jennifer C., University College London Institute of Child Health, London, London, United Kingdom
- Antonelou, Marilina, Royal Free Hospital, Dept of Nephrology, London, United Kingdom
- Henderson, Scott R., Royal Free Hospital, Dept of Nephrology, London, United Kingdom
- Long, David A., University College London Institute of Child Health, London, London, United Kingdom
- Pepper, Ruth, Royal Free Hospital, Dept of Nephrology, London, United Kingdom
Background
Focal segmental glomerulosclerosis (FSGS) is a disease that causes damage to podocytes, which form a key component of the glomerular filtration barrier. Mutations in multiple podocyte genes are associated with FSGS, but there is evidence that circulating factors can also induce podocyte damage, manifested as foot process effacement and disorganisation of the F-actin cytoskeleton. Treating FSGS patients with the experimental drug, Vincristine, has been effective in some cases, however, the biological effects in human podocytes are not well understood. The aim of this study is to investigate the effects of Vincristine treatment on podocytes using serum taken from a patient presenting with FSGS who showed full remission of disease with Vincristine treatment.
Methods
Human immortalised podocytes were treated with 10% patient serum at different time points of Vincristine treatment (disease presentation, on treatment and remission). Fetal bovine serum (FBS) and serum from a non-renal patient were used as controls. To determine a role for IgG in causing podocyte damage, some experiments were performed with IgG depleted from the presentation serum. Podocytes were stained with Phalloidin after 24 hours of serum treatment to examine the F-actin cytoskeleton.
Results
Podocytes treated with the presentation serum showed an increase in cell area, and a reorganisation of cortical F-actin fibres to cytoplasmic stress fibres, compared with podocytes treated with serum from the non-renal patient. This effect was still observed when IgG was depleted from the presentation serum. Podocytes treated with serum from when the patient was responding to Vincristine treatment showed no change in podocyte cell area or F-actin organisation compared with cells treated with serum from the non-renal patient. There was also no change to podocyte cell area or F-actin when podocytes were treated with the remission serum, when compared with the non-renal patient serum, suggesting Vincristine prevented podocyte damage.
Conclusion
Serum, but not IgG, from a patient with FSGS directly affects podocyte cell area and F-actin cytoskeleton in vitro. Vincristine prevents F-actin related podocyte damage, ultimately leading to a remission of FSGS.