Epithelial-Mesenchymal Transition in Liver Fibrosis

Epithelial-mesenchymal transition (EMT) describes a process by which liver epithelial cells––including hepatocytes and cholangiocytes––lose apical–basal polarity and intercellular adhesion, adopt a mesenchymal phenotype and contribute to the accumulation of collagen-secreting myofibroblasts. In chronic liver injury, sustained inflammation and cytokine release, particularly transforming growth factor-β (TGF-β), drive EMT alongside activation of resident hepatic stellate cells. The net result is excessive extracellular matrix deposition, progressive scarring and distortion of normal liver architecture. Lineage-tracing studies in rodent models have demonstrated that a fraction of myofibroblasts derive directly from hepatocyte EMT, while other work has highlighted a spectrum of partial EMT states and cell-state plasticity rather than a full conversion. Advances in single-cell transcriptomics and organoid co-culture systems reveal dynamic cross-talk among injured epithelial cells, stellate cells and inflammatory cells that both amplify profibrotic signalling and establish context-dependent repair programmes. The balance between EMT-driven fibrogenesis and compensatory regenerative responses underpins disease progression and highlights EMT as a potential therapeutic target to limit scarring and preserve liver function.

Research from Nature Portfolio

Recent studies have illuminated how profibrotic signalling intersects with redox regulation and hepatocyte plasticity. Work in models of alcoholic liver disease demonstrates that TGF-β1 and epidermal growth factor converge on the transcription factor ELK-3 to suppress α/β-hydrolase domain-containing 10 (ABHD10). ABHD10 loss promotes oxidative modification of the antioxidant peroxiredoxin 5, exacerbating hepatocyte dysfunction and fibrogenesis. Restoration of ABHD10 in vivo reduces oxidative stress, preserves hepatocyte phenotype and attenuates collagen accumulation. These findings reveal a novel axis whereby modulation of TGF-β signalling and cellular redox state influences epithelial-to-mesenchymal programmes and suggests that targeting the ELK-3–ABHD10 pathway may limit fibrotic remodelling.

Epithelial-Mesenchymal Transition in Liver Fibrosis publication trend

The graph below shows the total number of articles in epithelial-mesenchymal transition in liver fibrosis across all publications each year (not limited to Nature Index journals).

Technical terms

Epithelial-mesenchymal transition (EMT): A cellular programme in which epithelial cells lose polarity and adhesion, acquire mesenchymal traits such as motility and secrete extracellular matrix components.
Hepatic stellate cells (HSCs): Liver pericytes that, upon activation by injury signals, differentiate into collagen-producing myofibroblasts.
Myofibroblast: A contractile cell phenotype characterised by expression of α-smooth muscle actin and high extracellular matrix synthesis, central to fibrotic scarring.
Transforming growth factor-β (TGF-β): A profibrogenic cytokine that orchestrates cell activation, EMT and matrix deposition in chronic liver injury.
Extracellular matrix (ECM): A network of structural proteins, glycoproteins and proteoglycans deposited between cells, which becomes excessive in fibrosis.

References

1. The Elk-3 target Abhd10 ameliorates hepatotoxic injury and fibrosis in alcoholic liver disease. Communications Biology (2023).
2. Fibroblasts Derive from Hepatocytes in Liver Fibrosis via Epithelial to Mesenchymal Transition*. Journal of Biological Chemistry (2007).
3. Curcumin blunts epithelial-mesenchymal transition of hepatocytes to alleviate hepatic fibrosis through regulating oxidative stress and autophagy. Redox Biology (2020).
4. Imbalance in mitochondrial dynamics induced by low PGC-1α expression contributes to hepatocyte EMT and liver fibrosis. Cell Death & Disease (2020).
5. Mechanisms of fibrogenesis in liver cirrhosis: The molecular aspects of epithelial-mesenchymal transition. World Journal of Hepatology (2014).
6. Controversies over the Epithelial-to-Mesenchymal Transition in Liver Fibrosis. Journal of Clinical Medicine (2016).