2. Academic Validation
  3. Growth differentiation factor 15 is dispensable for acetaminophen-induced liver injury in mice

Growth differentiation factor 15 is dispensable for acetaminophen-induced liver injury in mice

  • Basic Clin Pharmacol Toxicol. 2023 Jan 5. doi: 10.1111/bcpt.13834.
Peng Jiang 1 2,  Zhenghong Liu 1,  Tingyu Fang 1,  Zhidan Zhang 1,  Yu Zhang 1,  Dongdong Wang 3,  Peter J Little 4 5,  Suowen Xu 1,  Jianping Weng 1
Affiliations

Affiliations

  • 1 Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, China.
  • 2 Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  • 3 Centre for Metabolism, Obesity and Diabetes Research and the Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
  • 4 School of Pharmacy, University of Queensland, Pharmacy Australia Centre of Excellence, Woolloongabba, Queensland, Australia.
  • 5 Sunshine Coast Health Institute and School of Health and Behavioural Sciences, University of the Sunshine Coast, Birtinya, Queensland, Australia.
PMID: 36602134 DOI: 10.1111/bcpt.13834
Abstract

Acetaminophen (APAP)-induced liver injury (AILI) has been recognized as a pivotal contributor to drug-induced liver failure in Western countries, but its molecular mechanism remains poorly understood. Growth Differentiation Factor 15 (GDF15) is a pleiotropic factor that alleviates non-alcoholic liver steatohepatitis, liver fibrosis and liver injury. The aim of the present study was to examine the possibility whether GDF15 confers protection against AILI. We found that the gene expression of Gdf15 was increased significantly after APAP overdose in mice. Next, the role of Gdf15 in AILI was evaluated by hepatic Gdf15 overexpression (using adeno-associated virus serotype 8), injection with recombinant human GDF15 (rhGDF15) and Gdf15 knockout mice after challenge with APAP. A marked elevation of Gdf15 was observed after AILI. However, there were no significant differences in AILI-related liver injury and JNK phosphorylation after Gdf15 overexpression, rhGDF15 injection or Gdf15 deficiency. Together, we conclude that, despite a noticeable elevation of Gdf15 level after AILI, Gdf15 is dispensable for APAP-induced AILI. Our study further suggests that genomic analysis of mRNA expression after APAP overdose is of limited relevance unless followed up by a functional analysis of candidate genes in vivo.

Keywords

AAV8; GDF15; acetaminophen; knockout; liver injury.

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