Related Experiment Video

Updated: May 2, 2026

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
09:44

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen

Published on: November 27, 2019

10.7K

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

Chih-Yun Lu1, Tsung-Hsuan Hsieh1, Min-Hui Chien1

  • 1Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Cell Biology and Toxicology
|May 1, 2026
PubMed

Insights

DNAJB4/HLJ1 deficiency worsens acetaminophen-induced liver injury by increasing endoplasmic reticulum stress. Restoring DNAJB4/HLJ1 expression protects against liver damage, suggesting it as a therapeutic target for drug-induced liver injury.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Cellular Stress Response

Background:

  • Drug-induced liver injury (DILI) is a major cause of acute liver failure, lacking reliable biomarkers and treatments.
  • Acetaminophen (APAP) overdose is the most frequent cause of DILI globally.
  • The role of Heat Shock Protein 40 family member DNAJB4/HLJ1 in APAP hepatotoxicity is unclear.

Purpose of the Study:

  • Investigate the function of DNAJB4/HLJ1 in APAP-induced liver injury using gene-deficient mice.
  • Elucidate the molecular mechanisms underlying DNAJB4/HLJ1's role in hepatotoxicity.
  • Assess DNAJB4/HLJ1 as a potential therapeutic target for DILI.

Main Methods:

  • Utilized DNAJB4/HLJ1-deficient mice (Dnajb4-/-) and wild-type controls (Dnajb4+/+).
  • Administered acetaminophen (APAP) and assessed liver injury markers, metabolic profiles, and gene expression.
  • Employed transcriptomic analysis, AlphaFold-Multimer modeling, and co-immunoprecipitation to study protein interactions and cellular pathways.
  • Investigated the role of endoplasmic reticulum (ER) stress and c-jun/JNK activation.

Main Results:

  • Dnajb4-/- mice showed exacerbated liver necrosis, elevated liver enzymes, and increased c-jun/JNK activation post-APAP.
  • Metabolic profiling revealed altered APAP metabolism, reduced detoxification, increased oxidative metabolites, and glutathione depletion in deficient mice.
  • Transcriptomic and molecular analyses confirmed aggravated ER stress and identified a physical interaction between DNAJB4/HLJ1 and HSP70.
  • Restoration of DNAJB4/HLJ1 attenuated ER stress, c-jun/JNK activation, and liver injury.

Conclusions:

  • DNAJB4/HLJ1 acts as a critical regulator of cellular stress signaling in APAP-induced hepatotoxicity.
  • DNAJB4/HLJ1 mitigates liver injury by modulating ER stress and promoting hepatocellular resilience.
  • DNAJB4/HLJ1 represents a promising therapeutic target for preventing or treating DILI.
Keywords:
AcetaminophenAcute liver failureDNAJB4Drug-induced liver injuryER stressHeat shock proteins

More Related Videos

Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms11:36

Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms

Published on: May 29, 2020

2.5K
Use of a Hanging-weight System for Liver Ischemia in Mice05:53

Use of a Hanging-weight System for Liver Ischemia in Mice

Published on: August 7, 2012

16.9K

Related Concept Videos

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
271
Hepatitis01:25

Hepatitis

Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver.
86
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
382
Liver Regeneration01:24

Liver Regeneration

The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
4.1K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.2K
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
94