{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE316nnn/GSE316475/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316475"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"E3 ubiquitin ligase RNF11 protects against liver ischemia reperfusion injury through HINT1 degradation-mediated PI3K/AKT activation","description":"Abstract Background: Liver ischemia reperfusion injury (IRI) is a major cause of postoperative liver dysfunction. RNF11, a conserved E3 ubiquitin ligase involved in inflammation, oxidative stress, and apoptosis, may be an important regulator of liver IRI.Methods: The role and mechanism of RNF11 in liver IRI were investigated using a mouse IRI model and AML12 hypoxia/reoxygenation (H/R) cells. RNF11 expressions were examined by RT-qPCR, Western blot, and immunohistochemistry. AAV- or lentivirus-mediated knockdown and overexpression were used to modulate RNF11. Liver injury was evaluated by serum biochemical parameters, histopathological changes, inflammatory cytokines, and apoptotic markers. RNA sequencing, KEGG analysis, co-immunoprecipitation, and ubiquitination assays were performed to explore mechanisms.Results: RNF11 expression was markedly downregulated in IRI livers and H/R-treated AML12 cells. RNF11 knockdown aggravated liver damage, with higher ALT/AST levels, increased necrosis, enhanced inflammatory infiltration, and upregulated proinflammatory cytokines, whereas RNF11 overexpression alleviated liver IRI in vivo and in vitro. RNF11 interacted with histidine triad nucleotide-binding protein 1 (HINT1) and activated PI3K/AKT signaling. The PI3K/AKT inhibitor LY294002 abrogated the anti-inflammatory and anti-apoptotic effects of RNF11. RNF11 promoted K48-linked polyubiquitination and proteasomal degradation of HINT1. Conclusion: RNF11 is a critical regulator of liver IRI that protects against inflammation and apoptosis by targeting HINT1 for K48-linked polyubiquitination and activating PI3K/AKT signaling, suggesting a potential therapeutic target for liver IRI.","dates":{"publication":"2026/04/30"},"accession":"GSE316475","cross_references":{"GSM":["GSM9453750","GSM9453751","GSM9453746","GSM9453749","GSM9453747","GSM9453748"],"GPL":["28330","28457"],"GSE":["316475"],"taxon":["Mus musculus"]}}