PXD064921

PXD064921 is an original dataset announced via ProteomeXchange.

Title	Targeting synergetic endothelial inflammation by inhibiting NFKB and JAK-STAT pathways
Description	Multiple systemic vascular inflammatory disorders are associated with endothelial dysfunction and elevated levels of TNFα and IFNγ. Combined TNFα and IFNγ stimulation induces synergetic hyperinflammation in endothelial cells (ECs) through activation of the NFKB and JAK/STAT pathways. Here we assess how targeting these pathways affects EC inflammation. Using mass-spectrometry based proteomics, we investigate system-wide effects of TNFα- and IFNγ-stimulated Endothelial Colony Forming Cells (ECFCs) in combination with inhibitors targeting NFKB and JAK/STAT pathways. JAK1 inhibitor itacitinib blocked IFNγ-, but not TNFα-induced proteomic responses. IKK2/STAT3 inhibitor TPCA1 attenuated both responses. Most TNFα+IFNγ-induced proteins, such as pyroptosis mediators, chemokines and Weibel-Palade Body content, were inhibited by both inhibitors, highlighting their synergetic dependency on both pathways. Imaging of Von Willebrand Factor (VWF) revealed an extracellular VWF network induced by combined stimulation; a phenotype which was reverted by both inhibitors. This study provides a mechanistic basis for inhibiting endothelial inflammation in vascular inflammatory disorders.
HostingRepository	PRIDE
AnnounceDate	2025-07-17
AnnouncementXML	Submission_2025-07-17_07:56:58.696.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stijn Groten
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-12 01:14:54	ID requested
⏵ 1	2025-07-17 07:56:59	announced

Dataset with its publication pending

submitter keyword: proteomics, inflammation, inhibitors,Endothelial cells

Maartje van den Biggelaar
contact affiliation	Proteomics Group, Department of molecular hemoastasis, Sanquin Research, Amsterdam, the Netherlands
contact email	m.vandenbiggelaar@sanquin.nl
lab head
Stijn Groten
contact affiliation	Sanquin Research
contact email	s.groten@sanquin.nl
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/2025/07/PXD064921

PRIDE project URI

• PRIDE
  1. PXD064921
     1. Label: PRIDE project
     2. Name: Targeting synergetic endothelial inflammation by inhibiting NFKB and JAK-STAT pathways