Omics · study · 2026
Platelet-derived S100A9 contributes to Endotheliopathy in Alcohol-Associated Hepatitis
Listed in NCBI GEO
Alcohol-associated liver disease (ALD) is a growing global health concern, with alcohol-associated hepatitis (AH) leading to the highest morbidity and mortality.
Description
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).
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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.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333389 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333389 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1471019 ncbi.nlm.nih.gov/bioproject/PRJNA1471019 ↗
project · from NCBI GEO
- PubMed 42635042 pubmed.ncbi.nlm.nih.gov/42635042 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE333389 | 10 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |