{"doi":"10.17615/tf68-7f41","title":"A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways","abstract":"Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl4)-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl4 (0.2 ml/kg 2×wk/6wks) followed by alcohol intragastrically (up to 25 g/kg/day for 3wks) and with continued CCl4. We observed that combined treatment with CCl4 and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for 53 damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Harcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways.","journal":"UNC Libraries","year":2020,"id":140649,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":299483,"name":"Ivan Rusyn","orcid":"0000-0001-9340-7384","position":1,"is_corresponding":false},{"id":548285,"name":"Hiroshi Kono","orcid":"0000-0001-6843-0814","position":2,"is_corresponding":false},{"id":546836,"name":"Takeki Uehara","orcid":"0000-0002-5853-9426","position":3,"is_corresponding":false},{"id":601888,"name":"Yasuhiro Iwata","orcid":null,"position":4,"is_corresponding":false},{"id":298735,"name":"Ramón Bataller","orcid":"0000-0002-1119-7799","position":5,"is_corresponding":false},{"id":599790,"name":"Grace A. Chappell","orcid":"0000-0002-7543-8336","position":6,"is_corresponding":false},{"id":605954,"name":"Shinji Furuya","orcid":null,"position":7,"is_corresponding":false},{"id":605478,"name":"Yuki Kato","orcid":"0000-0001-5616-2728","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:20.701143Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}