ArticleThe Journal of clinical investigation2020
Epithelial splicing regulatory protein 2-mediated alternative splicing reprograms hepatocytes in severe alcoholic hepatitis.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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Who cites it
49 citing papers in PubMed, 77 citations in OpenAlex.
- Autophagy in the liver.Autophagy reports · 2026Review
- An Update on Animal Models of Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- An Update on IL-22 Therapies in Alcohol-Associated Liver Disease and Beyond.The American journal of pathology · 2026Review
- Elevated Epithelial Splicing Regulatory Protein 1 Expression in Biliary Atresia Indicates Its Potential as a Molecular Marker.Biomolecules · 2025Article
- Identification of an IRF-ZBP1-caspase-8-NINJ1 axis in driving PANoptosis and pathology during alcohol-associated liver disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Derepression of the epithelial transcription factor GRHL2 promotes direct hepatocyte-to-cholangiocyte transdifferentiation.PLoS biology · 2025Article
- Alcohol-related hepatitis induces a specific fibrosis profile through YAP activation in myofibroblasts.JHEP reports : innovation in hepatology · 2025Article
- Early alternative splicing signatures and RBP networks in MASLD progression to cirrhosis.BMC medical genomics · 2025Article
- Aberrant alternative splicing in alcoholic hepatitis: regulatory roles of RBPs and sQTLs.BMC gastroenterology · 2025Article
- Dysregulated RNA splicing impairs regeneration in alcohol-associated liver disease.Nature communications · 2025Article
- Article
- Spatial gene regulatory networks driving cell state transitions during human liver disease.EMBO molecular medicine · 2025Article
- The critical role of the ZBP1-NINJ1 axis and IRF1/IRF9 in ethanol-induced cell death, PANoptosis, and alcohol-associated liver disease.bioRxiv : the preprint server for biology · 2025Article
- ESRP2-microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation.Genes & development · 2025Article
- Hepatic zinc deficiency dampens the acute phase response in patients with alcohol-associated hepatitis.Frontiers in immunology · 2025Article
- Pathogenesis of Alcohol-Associated Liver Disease.Clinics in liver disease · 2024Review
- KHSRP ameliorates acute liver failure by regulating pre-mRNA splicing through its interaction with SF3B1.Cell death & disease · 2024Article
- Proteomics identifies complement protein signatures in patients with alcohol-associated hepatitis.JCI insight · 2024Article
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
- Alcohol-associated liver disease.The Journal of clinical investigation · 2024Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
Abstract
Severe alcoholic hepatitis (SAH) is a deadly liver disease without an effective medical therapy. Although SAH mortality is known to correlate with hepatic accumulation of immature liver cells, why this occurs and how it causes death are unclear. Here, we demonstrate that expression of epithelial splicing regulatory protein 2 (ESRP2), an RNA-splicing factor that maintains the nonproliferative, mature phenotype of adult hepatocytes, was suppressed in both human SAH and various mouse models of SAH in parallel with the severity of alcohol consumption and liver damage. Inflammatory cytokines released by excessive alcohol ingestion reprogrammed adult hepatocytes into proliferative, fetal-like cells by suppressing ESRP2. Sustained loss of ESRP2 permitted reemergence of a fetal RNA-splicing program that attenuates the Hippo signaling pathway and thus allows fetal transcriptional regulators to accumulate in adult liver. We further showed that depleting ESRP2 in mice exacerbated alcohol-induced steatohepatitis, enabling surviving hepatocytes to shed adult hepatocyte functions and become more regenerative, but threatening overall survival by populating the liver with functionally immature hepatocytes. Our findings revealed a mechanism that explains why liver failure develops in patients with the clinical syndrome of SAH, suggesting that recovery from SAH might be improved by limiting adult-to-fetal reprogramming in hepatocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.