PXD028536

PXD028536 is an original dataset announced via ProteomeXchange.

Title	Idiopathic focal segmental glomerulosclerosis plasmas increase lipid droplet formation and perilipin-2 expression in human podocytes
Description	Background: Many patients with idiopathic focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation. Several circulating permeability factors (CPFs) responsible for recurrence have been suggested, but there is no consensus about the identity of CPFs in FSGS. We aimed to find proteins involved in the mechanism of action of the CPF(s) and/or potential biomarkers for the presence of CPF(s). Methods: Cultured human podocytes were exposed to plasma from patients with FSGS with presumed CPF(s), or from (disease) controls. Podocyte proteomes were analyzed by mass spectrometry and differentially expressed proteins were validated using flow cytometry, RT-PCR, and immunofluorescence. Changes in podocyte granularity were examined using flow cytometry, electron microscopy imaging and BODIPY staining. Results: Perilipin-2 protein expression was increased in podocytes exposed to presumed CPF-containing plasmas, which was related to disease state and capacity of plasma to induce granularity in podocytes. Elevated perilipin-2 levels were confirmed at protein and mRNA level. The granules observed in podocytes actually are lipid droplets. Importantly, increased perilipin-2 staining was also detected in glomeruli of the FSGS patients whose active disease plasmas induced lipid droplets in podocytes. Conclusions: Our study demonstrates that presumably CPF-containing plasma from FSGS patients alter podocyte lipid metabolism and increase perilipin-2 protein and lipid droplet accumulation. Future research should address the mechanism underlying CPF-induced alterations in podocyte lipid metabolism in the context of the pathogenesis of (recurrent) FSGS, which ultimately may result in novel leads for treatment.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:53:27.206.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guido van Mierlo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-16 06:42:45	ID requested
1	2022-12-22 03:32:19	announced
⏵ 2	2023-11-14 08:53:28	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Circulating permeability factor, podocytes, lipid droplets, perilipin-2, idiopathic focal segmental glomerulosclerosis (FSGS)

Michiel Vermeulen
contact affiliation	Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, The Netherlands
contact email	michiel.vermeulen@science.ru.nl
lab head
Guido van Mierlo
contact affiliation	Radboud University
contact email	guidovanmierlo@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/12/PXD028536

PRIDE project URI

• PRIDE
  1. PXD028536
     1. Label: PRIDE project
     2. Name: Idiopathic focal segmental glomerulosclerosis plasmas increase lipid droplet formation and perilipin-2 expression in human podocytes