Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes
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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.
in: INT J MOL SCI, Jahrgang 24, Nr. 1, 194, 22.12.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes
AU - den Braanker, Dirk J W
AU - Maas, Rutger J H
AU - van Mierlo, Guido
AU - Parr, Naomi M J
AU - Bakker-van Bebber, Marinka
AU - Deegens, Jeroen K J
AU - Jansen, Pascal W T C
AU - Gloerich, Jolein
AU - Willemsen, Brigith
AU - Dijkman, Henry B
AU - van Gool, Alain J
AU - Wetzels, Jack F M
AU - Rinschen, Markus M
AU - Vermeulen, Michiel
AU - Nijenhuis, Tom
AU - van der Vlag, Johan
PY - 2022/12/22
Y1 - 2022/12/22
N2 - 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.
AB - 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.
KW - Humans
KW - Podocytes/metabolism
KW - Glomerulosclerosis, Focal Segmental/metabolism
KW - Perilipin-2/genetics
KW - Lipid Droplets/metabolism
KW - Kidney Glomerulus/metabolism
KW - Biomarkers/metabolism
U2 - 10.3390/ijms24010194
DO - 10.3390/ijms24010194
M3 - SCORING: Journal article
C2 - 36613637
VL - 24
JO - INT J MOL SCI
JF - INT J MOL SCI
SN - 1661-6596
IS - 1
M1 - 194
ER -