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AIBP protects drug-induced liver injury by inhibiting MAPK-mediated NR4A1 expression

Tao Ma1,2, Wei Huang1, Yihong Ding1,3

  • 1Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China.

Iscience
|October 14, 2024
PubMed

Insights

Apolipoprotein A-I binding protein (AIBP) protects against drug-induced liver injury (DILI). Lower AIBP levels worsen liver damage, while higher levels offer protection by inhibiting MAPK pathways.

Area of Science:

  • Hepatology
  • Biochemistry
  • Molecular Biology

Background:

  • Drug-induced liver injury (DILI) is a significant adverse drug reaction with potentially fatal outcomes.
  • The role of Apolipoprotein A-I binding protein (AIBP) in DILI pathogenesis remains largely unexplored.
  • AIBP is implicated in lipid metabolism and mitochondrial function.

Purpose of the Study:

  • To investigate the role of AIBP in the development and progression of DILI.
  • To elucidate the molecular mechanisms by which AIBP influences hepatocyte injury.
  • To evaluate AIBP as a potential biomarker and therapeutic target for DILI.

Main Methods:

  • Established DILI animal models using AIBP knockout mice.
  • Utilized cell line models with AIBP overexpression and knockdown.
  • Employed western blotting and real-time qPCR to analyze MAPK signaling pathways and NR4A1 regulation.
  • Assessed hepatocyte viability and injury markers.

Main Results:

  • AIBP expression was significantly downregulated in hepatocytes during injury.
  • AIBP-deficient mice exhibited exacerbated liver injury and increased sensitivity to drug-induced cell death.
  • Overexpression of AIBP conferred protection against acetaminophen (APAP)-induced liver injury.
  • AIBP was found to inhibit MAPK pathway activation, regulating NR4A1 expression.

Conclusions:

  • AIBP plays a protective role in mitigating DILI.
  • AIBP functions by suppressing MAPK signaling pathways and modulating NR4A1.
  • AIBP represents a promising biomarker and therapeutic target for managing liver injury.
Keywords:
Biological sciencesNatural sciencesPathophysiologyPhysiology

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