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

Peng Jiang; Zhenghong Liu; Tingyu Fang; Zhidan Zhang; Yu Zhang; Dongdong Wang; Peter J Little; Suowen Xu; Jianping Weng

doi:10.1111/bcpt.13834

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

Journal article

Peer reviewed

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

Peng Jiang, Zhenghong Liu, Tingyu Fang, Zhidan Zhang, Yu Zhang, Dongdong Wang, Peter J Little, Suowen Xu and Jianping Weng

Basic & Clinical Pharmacology & Toxicology, Vol.132(4), pp.341-351

2023

DOI: https://doi.org/10.1111/bcpt.13834

PMID: 36602134

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Abstract

knockout

AAV8

Acetaminophen

GDF15

Liver injury

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 which 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.

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Title: Growth differentiation factor 15 is dispensable for acetaminophen (APAP)-induced liver injury in mice
Authors: Peng Jiang (Author) - University of Science and Technology of China
Zhenghong Liu (Author) - University of Science and Technology of China
Tingyu Fang (Author) - University of Science and Technology of China
Zhidan Zhang (Author) - University of Science and Technology of China
Yu Zhang (Author) - University of Science and Technology of China
Dongdong Wang (Author) - McMaster University
Peter J Little (Author) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - Legacy
Suowen Xu (Author) - University of Science and Technology of China
Jianping Weng (Author) - University of Science and Technology of China
Publication details: Basic & Clinical Pharmacology & Toxicology, Vol.132(4), pp.341-351
Publisher: Wiley-Blackwell Publishing Ltd.
DOI: 10.1111/bcpt.13834
ISSN: 1742-7843
PMID: 36602134
Organisation Unit: School of Health and Behavioural Sciences - Legacy; University of the Sunshine Coast, Queensland; School of Health
Language: English
Record Identifier: 99698698802621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Pharmacology & Pharmacy; Toxicology

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