PXD056096

PXD056096 is an original dataset announced via ProteomeXchange.

Title	Dynamic multi-omics and mechanistic modeling approach uncovers novel mechanisms of kidney fibrosis progression
Description	Kidney fibrosis, characterized by excessive extracellular matrix (ECM) deposition, is a progressive disease that, despite affecting 10% of the population, lacks specific treatments and suitable biomarkers. Aimed at unraveling disease mechanisms and identifying potential therapeutic targets, this study presents a comprehensive, time-resolved multi-omics analysis of kidney fibrosis using an in vitro model system based on human kidney PDGFRβ+ mesenchymal cells. Using computational network modeling we integrated transcriptomics, proteomics, phosphoproteomics, and secretomics with imaging of the extracellular matrix (ECM). We quantified over 14,000 biomolecules across seven time points following TGF-β stimulation, revealing distinct temporal patterns in the expression and activity of known and potential novel renal fibrosis markers and modulators. The resulting time-resolved multi-omic network models allowed us to propose mechanisms related to fibrosis progression through early transcriptional reprogramming. Using siRNA knockdowns and phenotypic assays, we validated predictions and elucidated regulatory mechanisms underlying kidney fibrosis. Notably, we demonstrate that several early-activated transcription factors, including FLI1 and E2F1, act as negative regulators of collagen deposition and propose underlying molecular mechanisms. This work advances our understanding of the pathogenesis of kidney fibrosis and provides a valuable resource for the organ fibrosis research community.
HostingRepository	PRIDE
AnnounceDate	2025-04-08
AnnouncementXML	Submission_2025-04-08_04:58:05.093.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frank Stein
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-23 08:35:21	ID requested
⏵ 1	2025-04-08 04:58:05	announced

Dataset with its publication pending

submitter keyword: time-points, network modeling, multi-omics, secretomics, proteomic, transcriptomics, phosphoproteomics,kidney fibrosis, extracellular matrix

Rainer Pepperkok
contact affiliation	European Molecular Biology Laboratory (EMBL) Meyerhofstr 17 69117 Heidelberg Germany
contact email	rainer.pepperkok@embl.org
lab head
Frank Stein
contact affiliation	EMBL
contact email	frank.stein@embl.de
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/2025/04/PXD056096

PRIDE project URI

• PRIDE
  1. PXD056096
     1. Label: PRIDE project
     2. Name: Dynamic multi-omics and mechanistic modeling approach uncovers novel mechanisms of kidney fibrosis progression