2. Academic Validation
  3. AIBP protects drug-induced liver injury by inhibiting MAPK-mediated NR4A1 expression

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

  • iScience. 2024 Sep 12;27(10):110873. doi: 10.1016/j.isci.2024.110873.
Tao Ma 1 2,  Wei Huang 1,  Yihong Ding 1 3,  Ran Ji 4,  Sijia Ge 1 2,  Qingqing Liu 1 2,  Yiheng Liu 1 2,  Jing Chen 1 2,  Yang Yan 1 2,  Shushu Lu 1 2,  Qiqi Ren 1 2,  Yihui Fan 5,  Renfang Mao 6,  Cuihua Lu 1
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China.
  • 2 Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, China.
  • 3 Department of Gastroenterology, Rugao People's Hospital, Nantong, Jiangsu, China.
  • 4 Department of Gastroenterology, Nantong First People's Hospital, Nantong, Jiangsu, China.
  • 5 Department of Pathogenic Biology, School of Medicine, Nantong University, Nantong, Jiangsu, China.
  • 6 Department of Pathophysiology, School of Medicine, Nantong University, Nantong, Jiangsu, China.
PMID: 39398235 DOI: 10.1016/j.isci.2024.110873
Abstract

Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. AIBP is a binding protein of apolipoprotein AI involved in lipid metabolism and maintenance of oxidative respiration in mitochondria, but its role in DILI is unclear. By constructing AIBP knockout mice, overexpressing and knocking down AIBP in cell lines, we established animal and cell models of DILI. Using western blotting and real-time qPCR assay, we explored the influence of AIBP in activation of mitogen-activated protein kinases (MAPK) signal pathways and possible targets. AIBP was downregulated during hepatocyte injury. AIBP deficient mice develop severe liver injury and more sensitive to drug-induced cell death. Overexpression of AIBP protects cells under APAP treatment. Furthermore, AIBP inhibits the activation of MAPK pathways, through which AIBP regulates NR4A1. These results suggest that AIBP is expected to become a valuable biomarker and therapeutic target in liver injury.

Keywords

Biological sciences; Natural sciences; Pathophysiology; Physiology.

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