{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE313nnn/GSE313271/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313271"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"S100A10-ANXA2 TETRAMER INHIBITION HAMPERS HEPATIC STELLATE CELL ACTIVATION IN MASLD MODELING HUMAN LIVER ORGANOIDS","description":"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. 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. 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.","dates":{"publication":"2026/04/16"},"accession":"GSE313271","cross_references":{"GSM":["GSM9365059"],"GPL":["24676"],"GSE":["313271"],"taxon":["Homo sapiens"]}}