Metalloprotease ADAM10 inhibition mitigates acute liver injury via repression of intrahepatic inflammation.

Weihua Cheng, Wei Meng, Yihai Gu

Minerva medica 2022 Jun

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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. ADAM10 loaded in adeno-associated viral vectors (AAV-ADAM10) or short hairpin RNA loaded in lentivirus aimed at murine ADAM10 mRNA (sh-RNA-ADAM10) were respectively delivered to mice via tail intravenous injection to achieve overexpression or silence of ADAM10. Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), immunohistochemical (IHC) and hematoxylin and eosin (HE) staining were conducted to measure ADAM10 alteration, inflammation level, histology and liver function. We show that the expression of ADAM10 markedly increases in CTC-induced injured liver tissues. Moreover, we demonstrate that the knockdown of ADAM10 attenuates the intrahepatic inflammation and protects hepatic histology and function in ALI mice; however, the overexpression of ADAM10 aggravates inflammation and liver lesion. The above suggested that the inhibition of ADAM10 ameliorates ALI through inhibiting inflammation. Our research provides novel view on the ADAM10 modulation of process of ALI by the inflammation aspect and verify a potential target for the therapy of ALI in the future.

Citation

Weihua Cheng, Wei Meng, Yihai Gu. Metalloprotease ADAM10 inhibition mitigates acute liver injury via repression of intrahepatic inflammation. Minerva medica. 2022 Jun;113(3):506-512