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Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes
Many patients with primary focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation. Several circulating permeability factors (CPFs) responsible for recurrence have been suggested, but were never validated. We aimed to find proteins involved in the mec...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820489/ https://www.ncbi.nlm.nih.gov/pubmed/36613637 http://dx.doi.org/10.3390/ijms24010194 |
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author | den Braanker, Dirk J. W. Maas, Rutger J. H. van Mierlo, Guido Parr, Naomi M. J. Bakker-van Bebber, Marinka Deegens, Jeroen K. J. Jansen, Pascal W. T. C. Gloerich, Jolein Willemsen, Brigith Dijkman, Henry B. van Gool, Alain J. Wetzels, Jack F. M. Rinschen, Markus M. Vermeulen, Michiel Nijenhuis, Tom van der Vlag, Johan |
author_facet | den Braanker, Dirk J. W. Maas, Rutger J. H. van Mierlo, Guido Parr, Naomi M. J. Bakker-van Bebber, Marinka Deegens, Jeroen K. J. Jansen, Pascal W. T. C. Gloerich, Jolein Willemsen, Brigith Dijkman, Henry B. van Gool, Alain J. Wetzels, Jack F. M. Rinschen, Markus M. Vermeulen, Michiel Nijenhuis, Tom van der Vlag, Johan |
author_sort | den Braanker, Dirk J. W. |
collection | PubMed |
description | Many patients with primary focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation. Several circulating permeability factors (CPFs) responsible for recurrence have been suggested, but were never validated. We aimed to find proteins involved in the mechanism of action of CPF(s) and/or potential biomarkers for the presence of CPF(s). Cultured human podocytes were exposed to plasma from patients with FSGS with presumed CPF(s) or healthy and disease controls. Podocyte proteomes were analyzed by LC–MS. Results were validated using flow cytometry, RT-PCR, and immunofluorescence. Podocyte granularity was examined using flow cytometry, electron microscopy imaging, and BODIPY staining. Perilipin-2 protein expression was increased in podocytes exposed to presumed CPF-containing plasmas, and correlated with the capacity of plasma to induce podocyte granularity, identified as lipid droplet accumulation. Elevated podocyte perilipin-2 was confirmed at protein and mRNA level and was also detected in glomeruli of FSGS patients whose active disease plasmas induced podocyte perilipin-2 and lipid droplets. Our study demonstrates that presumably, CPF-containing plasmas from FSGS patients induce podocyte lipid droplet accumulation and perilipin-2 expression, identifying perilipin-2 as a potential biomarker. Future research should address the mechanism underlying CPF-induced alterations in podocyte lipid metabolism, which ultimately may result in novel leads for treatment. |
format | Online Article Text |
id | pubmed-9820489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98204892023-01-07 Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes den Braanker, Dirk J. W. Maas, Rutger J. H. van Mierlo, Guido Parr, Naomi M. J. Bakker-van Bebber, Marinka Deegens, Jeroen K. J. Jansen, Pascal W. T. C. Gloerich, Jolein Willemsen, Brigith Dijkman, Henry B. van Gool, Alain J. Wetzels, Jack F. M. Rinschen, Markus M. Vermeulen, Michiel Nijenhuis, Tom van der Vlag, Johan Int J Mol Sci Article Many patients with primary focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation. Several circulating permeability factors (CPFs) responsible for recurrence have been suggested, but were never validated. We aimed to find proteins involved in the mechanism of action of CPF(s) and/or potential biomarkers for the presence of CPF(s). Cultured human podocytes were exposed to plasma from patients with FSGS with presumed CPF(s) or healthy and disease controls. Podocyte proteomes were analyzed by LC–MS. Results were validated using flow cytometry, RT-PCR, and immunofluorescence. Podocyte granularity was examined using flow cytometry, electron microscopy imaging, and BODIPY staining. Perilipin-2 protein expression was increased in podocytes exposed to presumed CPF-containing plasmas, and correlated with the capacity of plasma to induce podocyte granularity, identified as lipid droplet accumulation. Elevated podocyte perilipin-2 was confirmed at protein and mRNA level and was also detected in glomeruli of FSGS patients whose active disease plasmas induced podocyte perilipin-2 and lipid droplets. Our study demonstrates that presumably, CPF-containing plasmas from FSGS patients induce podocyte lipid droplet accumulation and perilipin-2 expression, identifying perilipin-2 as a potential biomarker. Future research should address the mechanism underlying CPF-induced alterations in podocyte lipid metabolism, which ultimately may result in novel leads for treatment. MDPI 2022-12-22 /pmc/articles/PMC9820489/ /pubmed/36613637 http://dx.doi.org/10.3390/ijms24010194 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article den Braanker, Dirk J. W. Maas, Rutger J. H. van Mierlo, Guido Parr, Naomi M. J. Bakker-van Bebber, Marinka Deegens, Jeroen K. J. Jansen, Pascal W. T. C. Gloerich, Jolein Willemsen, Brigith Dijkman, Henry B. van Gool, Alain J. Wetzels, Jack F. M. Rinschen, Markus M. Vermeulen, Michiel Nijenhuis, Tom van der Vlag, Johan Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes |
title | Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes |
title_full | Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes |
title_fullStr | Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes |
title_full_unstemmed | Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes |
title_short | Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes |
title_sort | primary focal segmental glomerulosclerosis plasmas increase lipid droplet formation and perilipin-2 expression in human podocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820489/ https://www.ncbi.nlm.nih.gov/pubmed/36613637 http://dx.doi.org/10.3390/ijms24010194 |
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