Mouse and cell study links TGF-β/p38 signaling to Mallory-Denk bodies and liver cell senescence
In two mouse liver models, an in vitro hepatocyte model and three human liver cancer specimens, the TGF-β/p38 axis was associated with Mallory-Denk body formation and features of hepatocellular senescence; inhibiting p38 in cells reduced both. [1]
Automatic summary · not editorially reviewed
The key findings
Two MDB-positive mouse models were used: a high-fat-diet plus DDC steatohepatitis model and a carbon-tetrachloride plus DDC liver fibrosis model, alongside an in vitro hepatocyte model and three human liver cancer specimens. [1]
Both animal models showed MDB formation, metabolic dysregulation and liver fibrosis with activated p38 signaling, increased p-K8 S73 and features of hepatocellular senescence. [1]
In vitro p38 inhibition reduced p-K8 S73, suppressed MDB formation and attenuated the senescent phenotype; the authors suggest the axis may be a common mechanism. [1]
The source at a glance
- Study type / format
- Preclinical animal and cell study with three human specimens (abstract)
- Population / context
- Two mouse liver models, an in vitro hepatocyte model and three human hepatocellular carcinoma specimens
- Summary based on
- Study abstract
- Original publication
- October 1, 2026
Mouse liver models and human tumor samples studied
The researchers asked whether the TGF-β/p38 signaling axis is a shared pathway driving both Mallory-Denk body (MDB) formation and hepatocellular senescence. They used two MDB-positive mouse models: a steatohepatitis model induced by a high-fat diet plus DDC, and a liver fibrosis model induced by carbon tetrachloride plus DDC. An in vitro MDB-forming hepatocyte model stimulated with TNF-α/IFN-γ and TGF-β complemented these, and three human hepatocellular carcinoma specimens with abundant MDBs were analyzed.
Supporting source [1]
p38 activation, keratin change and senescence features in models
Both animal models showed MDB formation, metabolic dysregulation and liver fibrosis, together with activated p38 signaling, increased phosphorylation of keratin 8 at serine 73 (p-K8 S73) and features of hepatocellular senescence. RNA sequencing of the high-fat-diet plus DDC steatohepatitis model implicated p38 signaling in MDB formation and cellular senescence at the transcriptomic level. p38 activation was also confirmed in the human liver cancer specimens. In vitro, pharmacological p38 inhibition lowered p-K8 S73, suppressed MDB formation and attenuated the senescent phenotype.
Supporting source [1]
Suggested shared mechanism, not proven cause in humans
The authors conclude that the TGF-β/p38 axis may be a common molecular mechanism behind both MDB formation and hepatocellular senescence, offering insights into MDB-associated liver disease. This is a suggested mechanism, not proof of cause. The human material was only three liver cancer specimens, and the animal and cell findings do not establish benefit for human lifespan or disease outcomes. Only the abstract was reviewed; the full text was not reviewed.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Human evidence comes from three liver cancer specimens. Findings are associations in mice and cells, not proof of cause or of human lifespan or disease benefit.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Luo X, Huang M, Luo X, Shi Y, Dang Z, Zhao Y, Chen D, Zhan Y, Zhong B, He F, Liu H. · europepmc.org · October 1, 2026