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Minerva Medica 2020 Jun 05

DOI: 10.23736/S0026-4806.20.06655-0

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

Metalloprotease Adam10 inhibition mitigates acute liver injury via repression of intrahepatic inflammation

Weihua CHENG 1, Wei MENG 2, Yihai GU 3

1 Departments of Hepatobiliary, Pancreatic and Splenic Surgery, Baoji Central Hospital, Baoji, China; 2 Department of Infectious Disease, Binzhou People's Hospital, Binzhou, China; 3 Department of Traditional Chinese Medicine, Sixth People's Hospital of Qingdao, Qingdao, China


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BACKGROUND: Acute liver injury (ALI) is associated with the occurrence and progress of intrahepatic inflammation. Recent studies have shown that Adam10, a significant member of metalloproteinase family, has modulated the inflammation level in various neurologic diseases. However, it is elusive whether Adam10 regulation exert a hepatic protective effect on ALI by the suppression of inflammation level. The study aimed to explore the regulated function of Adam10 on acute liver injury.
METHODS: C57BL/6J mice (eight-week-old, male) were carried out intraperitoneal injection of tetrachloromethane (CTC) to provoke ALI. Adam 10 loaded in Adeno-associated viral vectors (AAV-Adam 10) or short hairpin RNA loaded in lentivirus aimed at murine Adam 10 mRNA (sh-RNA-Adam 10) were respectively delivered to mice via tail intravenous injection to achieve overexpression or silence of Adam 10. Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), immumohistochemical (IHC) and hematoxylin and eosin (HE) staining were conducted to measure Adam 10 alteration, inflammation level, histology and liver function.
RESULTS: We show that the expression of Adam 10 markedly increases in CTC-induced injured liver tissues. Moreover, we demonstrate that the knockdown of Adam 10 attenuates the intrahepatic inflammation and protects hepatic histology and function in ALI mice, however the overexpression of Adam10 aggravates inflammation and liver lesion.
CONCLUSIONS: The above suggested that the inhibition of Adam 10 ameliorates ALI through inhibiting inflammation. Our research provides novel view on the Adam 10 modulation of process of ALI by the inflammation aspect and verify a potential target for the therapy of ALI in the future.


KEY WORDS: Adam 10; Metalloprotease; Acute liver injury; Inflammation; Liver function

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