PXD065854

PXD065854 is an original dataset announced via ProteomeXchange.

Title	The function of the Receptor for Advanced Glycation End Products (RAGE) in ductular reaction-mediated liver fibrosis during cholestasis
Description	Ductular reaction (DR) is the hallmark of cholestatic diseases manifested in the proliferation of bile ductules lined by biliary epithelial cells (BECs). It is commonly associated with increased risk of fibrosis and liver failure. The Receptor for Advanced Glycation End Products (RAGE) was identified as a critical mediator of DR during chronic injury. Yet, the direct link between RAGE-mediated DR and fibrosis as well as the mode of interaction between BECs and hepatic stellate cells (HSCs) to drive fibrosis remain elusive. Here, we delineate the specific function of RAGE on BECs during DR and its potential association with fibrosis in the context of cholestasis. Employing a biliary lineage tracing cholestatic liver injury mouse model, combined with whole transcriptome sequencing, mass spectrometry and in vitro analyses, we investigated the role for BEC-specific Rage activity in fostering a pro-fibrotic milieu. RAGE is predominantly expressed in BECs and contributes to DR. Employing mass spectrometry analyses of soluble factors of in vitro cultured wildtype and RAGE deficient BECs Notch ligand Jagged1 was found to be secreted from activated BECs in a Rage-dependent manner and signals HSCs in trans, eventually enhancing fibrosis during cholestasis.
HostingRepository	PRIDE
AnnounceDate	2025-07-16
AnnouncementXML	Submission_2025-07-16_02:15:10.199.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peter Angel
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-07 09:55:10	ID requested
⏵ 1	2025-07-16 02:15:10	announced

10.1038/S44319-024-00356-7;

submitter keyword: biliary epithelial cells Chronic liver injury Genetically modified mice Hepatic Stellate Cells Receptor for Advanced Glycation End Products

Peter Angel
contact affiliation	German Cancer Research Center (DKFZ)
contact email	p.angel@dkfz.de
lab head
Peter Angel
contact affiliation	German Cancer Research Center (DKFZ)
contact email	p.angel@dkfz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065854
     1. Label: PRIDE project
     2. Name: The function of the Receptor for Advanced Glycation End Products (RAGE) in ductular reaction-mediated liver fibrosis during cholestasis