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PXD056096-1

PXD056096 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDynamic multi-omics and mechanistic modeling approach uncovers novel mechanisms of kidney fibrosis progression
DescriptionKidney 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.
HostingRepositoryPRIDE
AnnounceDate2025-04-08
AnnouncementXMLSubmission_2025-04-08_04:58:05.093.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFrank Stein
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-09-23 08:35:21ID requested
12025-04-08 04:58:05announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: time-points, network modeling, multi-omics, secretomics, proteomic, transcriptomics, phosphoproteomics,kidney fibrosis, extracellular matrix
Contact List
Rainer Pepperkok
contact affiliationEuropean Molecular Biology Laboratory (EMBL) Meyerhofstr 17 69117 Heidelberg Germany
contact emailrainer.pepperkok@embl.org
lab head
Frank Stein
contact affiliationEMBL
contact emailfrank.stein@embl.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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