Human hepatocyte-derived extracellular vesicles attenuate the carbon tetrachloride-induced acute liver injury in mice

• Published in: Cell death & disease Vol. 12; no. 11; pp. 1010 - 12
• Main Authors: Kakizaki, Masatoshi, Yamamoto, Yuichiro, Nakayama, Shunya, Kameda, Kazuaki, Nagashima, Etsuko, Ito, Masatoshi, Suyama, Takashi, Matsuzaki, Yumi, Chiba, Tetsuhiro, Sumiyoshi, Hideaki, Inagaki, Yutaka, Kotani, Ai
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.10.2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/21; 14/1; 14/19; 45/77; 45/90; 631/250/256/2516; 64/60; 692/699/1503/1607; 82/58; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; Bone marrow; Carbon tetrachloride; Carbon Tetrachloride - adverse effects; CCL4 protein; Cell Biology; Cell Culture; Cell interactions; Chemokine receptors; Chemokines; Extracellular vesicles; Extracellular Vesicles - metabolism; Female; Graft rejection; Hepatocytes; Hepatocytes - metabolism; Humans; Immune response; Immunology; Leukocytes (neutrophilic); Life Sciences; Lipids; Liver; Liver diseases; Liver Failure, Acute - chemically induced; Liver transplantation; Mice; Monocytes
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-04204-7

Acute liver injury (ALI) induced by chemicals or viruses can progress rapidly to acute liver failure (ALF), often resulting in death of patients without liver transplantation. Since liver transplantation is limited due to a paucity of donors, expensive surgical costs, and severe immune rejection, novel therapies are required to treat liver injury. Extracellular vesicles (EVs) are used for cellular communication, carrying RNAs, proteins, and lipids and delivering them intercellularly after being endocytosed by target cells. Recently, it was reported that EVs secreted from human hepatocytes have an ability to modulate the immune responses; however, these roles of EVs secreted from human hepatocytes were studied only with in vitro experiments. In the present study, we evidenced that EVs secreted from human hepatocytes attenuated the CCL 4 -induced ALI by inhibiting the recruitment of monocytes through downregulation of chemokine receptor in the bone marrow and recruitment of neutrophils through the reduction of C-X-C motif chemokine ligand 1 (CXCL1) and CXCL2 expression levels in the liver.