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May 3, 20260 citations

DNAJB4/HLJ1 protects against acetaminophen-induced liver injury by attenuating ER stress via HSP70.

CLChih-Yun LuNational Taiwan University THTsung-Hsuan HsiehNational Taiwan University MCMin-Hui ChienNational Taiwan University

Key Points

This research aims to explore how DNAJB4/HLJ1 protects against acetaminophen-induced liver injury by reducing endoplasmic reticulum (ER) stress.
AlphaFold-Multimer modeling and co-immunoprecipitation were used to validate the interaction between DNAJB4/HLJ1 and HSP70.
Restoration of DNAJB4/HLJ1 expression was conducted to examine its effects on ER stress, c-jun/JNK activation, and liver injury.
Pharmacological inhibition of ER stress was utilized to confirm its role in liver damage mitigation.
Restoration of DNAJB4/HLJ1 expression reduced ER stress and liver injury significantly.
Pharmacological inhibition of ER stress resulted in decreased c-jun/JNK activation, indicating a protective effect.
Identify DNAJB4/HLJ1 as a key regulator in addressing acetaminophen-induced hepatotoxicity.

Abstract

livers. AlphaFold-Multimer modeling and co-immunoprecipitation validated physical interaction between DNAJB4/HLJ1 and HSP70. Restoration of DNAJB4/HLJ1 expression attenuated ER stress, c-jun/JNK activation, and liver injury, while pharmacological inhibition of ER stress confirmed its mechanistic involvement. Collectively, these findings identify DNAJB4/HLJ1 as a previously unrecognized regulator of stress signaling in APAP-induced hepatotoxicity. By modulating ER stress within the integrated cellular stress network, DNAJB4/HLJ1 limits injury progression and promotes hepatocellular resilience, highlighting its potential as a novel therapeutic target for preventing or mitigating DILI.

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