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

Minerva medica
Weihua ChengYihai Gu

Abstract

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. 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. We show that the expression of Adam 10 markedly increases in CTC-induced injured liver tissues. More...Continue Reading

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