ArticleGut2026
Zinc-dependent RNA-binding protein controls hepatocyte senescence and recovery from alcohol-related liver failure.
Article in Gut, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
backgroundWhy alcohol-associated liver disease (ALD) resolves after abstinence in most people but progresses to liver failure in others remains poorly understood. Experimental models show that increased exposure to proinflammatory cytokines exacerbates ALD, yet clinical trials targeting these cytokines have failed. The tumour necrosis factor alpha (TNFα)-inducible zinc finger protein 36 (ZFP 36) family of RNA binding proteins controls the outcomes of TNFα exposure by destabilising suites of messenger RNAs (mRNAs) that execute the pleiotropic downstream actions of TNFα.
objectiveTo investigate the role of RNA binding protein ZFP36 ring finger protein like 1 (ZFP36L1) in regulating hepatocyte fate and its contribution to the progression of ALD.
designWe selectively deleted ZFP36L1 in mouse hepatocytes to assess its impact on ALD progression, transcriptional reprogramming, senescence and direct mRNA targets. In parallel, we analysed human liver explants to evaluate ZFP36L1 in relation to hepatocyte senescence, disease severity and zinc-dependent regulation.
resultsDeletion of ZFP36L1 exacerbated experimental ALD and activated transcriptional programmes driving ductal transdifferentiation, inflammation and senescence. Mechanistically, ZFP36L1 directly destabilised cyclin-dependent kinase inhibitor 1A (Cdkn1a)(p21) and jagged canonical notch ligand 1 (Jag1) mRNAs, thereby suppressing hepatocyte senescence and JAG1-NOTCH signalling. In human liver explants, ZFP36L1 activity declined in parallel with increasing hepatocyte senescence and ALD severity and was closely associated with impaired zinc-dependent signalling. Manipulation of zinc availability altered ZFP36L1 activity and expression of its direct targets.
conclusionThese findings uncover a zinc-dependent ZFP36L1-regulon that governs hepatocyte fate by repressing p21- and JAG1-driven senescence and NOTCH activation and highlight ZFP36L1 as a promising therapeutic target in ALD.
Indexed as
Identifiers
What OpenQuestion holds
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.