Exogenous exosomes from mice with acetaminophen-induced liver injury promote toxicity in the recipient hepatocytes and mice

Young Eun Cho, Wonhyo Seo, Do Kyun Kim, Pyong Gon Moon, Sang Hyun Kim, Byung Heon Lee, Byoung Joon Song, Moon Chang Baek

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37 Scopus citations


Exosomes are small extracellular membrane vesicles released from endosomes of various cells and could be found in most body fluids. The main functions of exosomes have been recognized as important mediators of intercellular communication and as potential biomarkers of various disease states. This study investigated whether exogenous exosomes from mice with acetaminophen (APAP)-induced liver injury can damage the recipient hepatic cells or promote hepatotoxicity in mice. We observed that exogenous exosomes derived from APAP-exposed mice were internalized into the primary mouse hepatocytes or HepG2 hepatoma cells and significantly decreased the viability of these recipient cells. They also elevated mRNA transcripts and proteins associated with the cell death signaling pathways in primary hepatocytes or HepG2 cells via exosomes-to-cell communications. In addition, confocal microscopy of ex vivo liver section showed that exogenously added exosomes were accumulated in recipient hepatocytes. Furthermore, plasma reactive oxygen species and hepatic TNF-α/IL-1β production were elevated in APAP-exosomes recipient mice compared to control-exosomes recipient mice. The levels of apoptosis-related proteins such as phospho-JNK/JNK, Bax, and cleaved caspase-3 were increased in mouse liver received APAP-exosomes. These results demonstrate that exogenous exosomes from APAP-exposed mice with acute liver injury are functional and stimulate cell death or toxicity of the recipient hepatocytes and mice.

Original languageEnglish
Article number16070
JournalScientific Reports
Issue number1
StatePublished - 1 Dec 2018

Bibliographical note

Funding Information:
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2017M3A9G 80833382), by an NRF grant funded by the Korea government (2014R1A5A2009242), and by the Intramural Program of the National Institute on Alcohol Abuse and Alcoholism. YEC was supported by the Korean Biomedical Scientist Fellowship Program sponsored by Korean Research Institute of Bioscience and Biotechnology. Finally, the authors are grateful to Dr. Klaus Gawrisch for his support of this research project.

Publisher Copyright:
© 2018, The Author(s).


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