Journal Article

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

Shinji Takai, Denan Jin

2020

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Blood pressure / Chymases / Chymases - antagonists & inhibitors / Chymases - metabolism / Enzyme Inhibitors / Enzyme Inhibitors - pharmacology / Enzyme Inhibitors - therapeutic use / Enzymes / Fatty liver / Gene expression / Hepatitis / Humans / Hypertension / Inflammation / Liver / Liver - drug effects / Liver - enzymology / Liver diseases / Metabolic syndrome / Neutrophils / Non-alcoholic Fatty Liver Disease / Non-alcoholic Fatty Liver Disease - drug therapy / Non-alcoholic Fatty Liver Disease - metabolism / Oxidative stress / Peptides / Plasma / Pulmonary fibrosis / Review / Small intestine