Omics · study · 2026
S100A10-ANXA2 TETRAMER INHIBITION HAMPERS HEPATIC STELLATE CELL ACTIVATION IN MASLD MODELING HUMAN LIVER ORGANOIDS
Listed in NCBI GEO
Metabolic dysfunction-associated steatotic liver disease (MASLD), which begins with the pathological lipid accumulation within hepatocytes, can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by inflammation and fibrosis.
Description
Fibrosis is the strongest predictor of liver-related mortality, yet effective antifibrotic therapies remain limited, underscoring the need for new molecular targets.
Our previous work identified S100A10 as a MASLD promoter, suggesting that its association with Annexin A2 (ANXA2) within the S100A10-ANXA2 heterotetramer (A2t) might promote hepatic fibrosis. Here, we inhibited A2t using its specific inhibitor, A2ti-1, in human hepatic stellate cells (LX-2) and in human multilineage liver organoids (HLOs) modeling MASLD. A2ti-1 reduced α-SMA protein levels and decreased expression of profibrotic genes in LX-2 cells by directly suppression of stellate cell activation.
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In HLOs, A2ti-1 significantly attenuated fibrosis by reducing α-SMA expression, collagen deposition, and profibrotic genes, without altering steatosis. Mechanistically, A2ti-1 inhibited LX-2 activation through reducing STAT3 phosphorylation independently of SMAD signaling. These findings identify A2t as a previously unrecognized regulator of hepatic fibrosis and establish its pharmacological inhibition as a promising antifibrotic therapeutic strategy in MASH.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE313nnn/GSE313271 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313271 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1378869 ncbi.nlm.nih.gov/bioproject/PRJNA1378869 ↗
project · 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 | GSE313271 | 12 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 |