ArticleNature metabolism2025
A non-apoptotic caspase-8-meteorin pathway in hepatocytes promotes MASH fibrosis.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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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.
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Who cites it
5 citing papers in PubMed.
- Multi-omics and experimental evidence in human chondrocytes identify caspase-8 as a non-apoptotic regulator of inflammatory, senescent, and fibrotic signaling in osteoarthritis.Cell communication and signaling : CCS · 2026Article
- Metrnl in diabetes and its complications: divergent evidence and translational prospects.Journal of translational medicine · 2026Review
- Modulation of metabolic, inflammatory, fibrotic, and cell death pathways by resmetirom in metabolic dysfunction-associated steatohepatitis (MASH): a transcriptomic profiling study.Acta pharmacologica Sinica · 2026Article
- [Advances in basic and experimental diagnostic research on liver diseases in 2025].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Article
- Hepatocyte-hepatic stellate cell interactions in liver fibrosis: Mechanisms and therapeutic implications.Hepatology communications · 2026Review
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Authors and funding
14 authors.
Funding
Abstract
Metabolic-dysfunction-associated steatohepatitis (MASH) is the leading cause of chronic liver disease, but an incomplete understanding of MASH-induced liver fibrosis has limited therapeutic options. Here we show that hepatocyte caspase-8 drives MASH fibrosis through an apoptosis-independent mechanism. Hepatic caspase-8 expression correlates with liver fibrosis in both human and experimental MASH, and hepatocyte-specific caspase-8 deletion in male mice with MASH suppressed liver fibrosis and hepatic stellate cell (HSC) activation without affecting hepatocyte apoptosis. Mechanistic studies showed that a caspase-8-YY1 pathway in hepatocytes induces secretory meteorin (Metrn), which activates HSCs via a c-Kit-STAT3 pathway. Meteorin expression was increased in human and male mouse MASH livers and decreased by deletion of hepatocyte caspase-8 in MASH mice and human and mouse primary hepatocytes. Genetic restoration of hepatocyte meteorin in hepatocyte-caspase-8-deleted MASH mice restored HSC activation and liver fibrosis while silencing hepatocyte meteorin lowered liver fibrosis. These findings reveal a therapeutically targetable pathway promoting MASH fibrosis involving a non-apoptotic function of caspase-8 and a newly discovered HSC activator, meteorin.
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