PXD053109-1

PXD053109 is an original dataset announced via ProteomeXchange.

Title	Alcohol-associated hepatitis induces hepatocyte senescence which is reduced following disease resolution
Description	Background & Aims: Alcohol-associated hepatitis (AH) is an acute form of alcohol-related liver disease (ArLD) with high mortality rate. AH is histologically characterised by cellular processes including steatosis, inflammation and cell death. Apoptosis is the most studied form of cell death in AH; however, the role of cellular senescence, another response to cellular injury, in AH is unknown. Here we aim to explore the mechanisms of ArLD pathophysiology and define the role of senescence in AH. Methods: We performed RNA sequencing and bioinformatics analysis of transjugular liver biopsies (n=65) from AH patients participating in the ISAIAH clinical trial. We also carried out multiomic analysis of an in vitro hepatocyte model of AH. We also performed additional bioinformatics reanalysis of existing AH transcriptomic datasets. Results: Senescence markers and pathways are increasingly expressed in hepatocytes as ArLD progresses towards AH. We find dysregulation of senescence, inflammation and hepatocyte function is reversed at transcriptomic level following AH resolution. We identify dysregulation of two senescence-associated protein complexes, cytochrome c oxidase and the proteasome, which may act as senescence-induction mechanisms. Our in vitro model reveals senescence induction is a direct effect of ethanol on hepatocytes. Conclusions: Our results show a central role for senescence in AH and suggest senolytics as potential therapeutics in early ALD to limit AH severity.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-24_16:44:32.218.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex von Kriegsheim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-14 03:55:07	ID requested
⏵ 1	2025-08-24 16:44:33	announced

10.1136/gutjnl-2024-334094;

Rodrigo-Torres D, Kilpatrick AM, Ferreira-Gonzalez S, Aird RE, Atkinson SR, Gadd VL, Man TY, Tyson LD, Dhondalay GKR, Vergis N, Arteel GE, Thursz MR, Martinez-Gili L, Forbes SJ, Longitudinal paired liver biopsies and transcriptome profiling in alcohol-associated hepatitis reveal dynamic changes in cellular senescence. Gut, 74(9):1500-1513(2025) [pubmed]

submitter keyword: Liver, hepatocyte, alcohol

Stuart Forbes
contact affiliation	University of Edinburgh
contact email	stuart.forbes@ed.ac.uk
lab head
Alex von Kriegsheim
contact affiliation	University of Edinburgh
contact email	alex.vonkriegsheim@ed.ac.uk
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/2025/08/PXD053109

PRIDE project URI

• PRIDE
  1. PXD053109
     1. Label: PRIDE project
     2. Name: Alcohol-associated hepatitis induces hepatocyte senescence which is reduced following disease resolution