PXD078511

PXD078511 is an original dataset announced via ProteomeXchange.

Title	Platelet derived S100A9 contributes to Endotheliopathy in Alcohol-Associated Hepatitis
Description	Alcohol-associated liver disease (ALD) is a growing global health concern, with alcohol-associated hepatitis (AH) leading to the highest morbidity and mortality. Available therapies are limited and often inadequate. Platelets contribute in a variety of ways to the pathogenesis of liver diseases, but their role in AH remains largely unexplored. In this study we address the hypothesis that platelets contribute to pathological inflammation in AH. Using patient samples and a multi-omics approach, we found that platelets undergo proinflammatory transcriptomic and proteomic changes in AH, with two alarmins, S100A8 and S100A9, being among the top upregulated genes/proteins. Additionally, the abundance of platelet-derived microparticles containing S100A8 and S100A9 in AH patient plasma was increased (p=0.032) and correlated with disease severity (MELD-Na, r=0.51, p=0.03) and endotheliopathy (ICAM1, r=0.70, p=0.001) (CXCL8, r=0.48, p=0.04) (vWF, r=0.59, p=0.01). We mechanistically linked S100A9 with endotheliopathy via crosstalk between primary human liver sinusoidal endothelial cells and primary human monocytes. We also demonstrate that Interleukin-6 (IL6) upregulates S100A9 in megakaryocytic cells in a JAK/STAT-dependent manner, modeling changes occurring in the bone marrow in patients with AH. Our studies establish proinflammatory platelets as important contributors to AH disease pathology. Moreover, anti-platelet agents, or more specifically S100A9 targeted drugs, are potential therapeutic strategies in AH.
HostingRepository	PRIDE
AnnounceDate	2026-06-26
AnnouncementXML	Submission_2026-06-26_11:42:08.579.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	TuKiet Lam
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-18 11:52:04	ID requested
⏵ 1	2026-06-26 11:42:09	announced

Dataset with its publication pending

submitter keyword: Endothelial Cells, Alcohol-Associated Hepatitis, Endotheliopathy,Platelets

TuKiet Lam
contact affiliation	Keck MS & Proteomics Resource at Yale School of Medicine
contact email	tukiet.lam@yale.edu
lab head
TuKiet Lam
contact affiliation	Yale University
contact email	tukiet.lam@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD078511
     1. Label: PRIDE project
     2. Name: Platelet derived S100A9 contributes to Endotheliopathy in Alcohol-Associated Hepatitis