Chymase as a Possible Therapeutic Target for Amelioration of Non-Alcoholic Steatohepatitis

International Journal of Molecular Sciences

Shinji Takai¹  Denan Jin¹ 

[1] Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan;

关键词: non-alcoholic steatohepatitis;    inflammation;    fibrosis;    chymase;    inhibitor;   

DOI  :  10.3390/ijms21207543

来源: DOAJ

【 摘 要 】

The development and progression of non-alcoholic steatohepatitis (NASH) are linked to oxidative stress, inflammation, and fibrosis of the liver. Chymase, a chymotrypsin-like enzyme produced in mast cells, has various enzymatic actions. These actions include activation of angiotensin II, matrix metalloproteinase (MMP)-9, and transforming growth factor (TGF)-β, which are associated with oxidative stress, inflammation, and fibrosis, respectively. Augmentation of chymase activity in the liver has been reported in various NASH models. Generation of hepatic angiotensin II and related oxidative stress is upregulated in NASH but attenuated by treatment with a chymase inhibitor. Additionally, increases in MMP-9 and accumulation of inflammatory cells are observed in NASH but are decreased by chymase inhibitor administration. TGF-β and collagen I upregulation in NASH is also attenuated by chymase inhibition. These results in experimental NASH models demonstrate that a chymase inhibitor can effectively ameliorate NASH via the reduction of oxidative stress, inflammation, and fibrosis. Thus, chymase may be a therapeutic target for amelioration of NASH.

【 授权许可】

Unknown