Elevated HSP70 Ameliorates Liver Failure Patients via Its Novel Natural Inhibitor

Area of Science:

• Hepatology and immunology
• Molecular biology
• Biomarker discovery

Background:

• Liver failure results from severe hepatocyte injury, lacking effective biomarkers and treatments.
• Heat shock protein 70 (HSP70) is involved in cellular stress and inflammation, but its specific role in liver failure is not well understood.

Purpose of the Study:

• To elucidate the mechanistic role of HSP70 in liver failure.
• To evaluate HSP70 as a potential therapeutic target for liver failure.

Main Methods:

• Analysis of HSP70 levels in liver failure patients and correlation with clinical outcomes.
• Investigation of HSP70's biological function using a GalN/LPS-induced mouse model of liver failure.
• Assessment of therapeutic interventions including HSP70 inhibition and a natural compound, aPPD.

Main Results:

• HSP70 was significantly elevated in liver failure patients and correlated with disease severity markers like ALT and pro-inflammatory cytokines.
• In mice, HSP70 inhibition reduced liver injury, while exogenous HSP70 exacerbated it by promoting inflammation.
• The HSP70 inhibitor blocked TNF-α-induced apoptosis via the NF-κB pathway.
• Ginseng metabolite aPPD inhibited HSP70, significantly reducing liver failure severity and mortality in mice.

Conclusions:

• HSP70 plays a critical immunopathologic role in liver failure, representing a viable therapeutic target.
• The natural HSP70 inhibitor aPPD demonstrates significant protective effects, suggesting its potential as a novel treatment for liver failure.