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Front. Pharmacol. | doi: 10.3389/fphar.2018.00144

Chymase inhibitor as a novel therapeutic agent for non-alcoholic steatohepatitis

  • 1Innovative Medicine, Osaka Medical College, Japan

Non-alcoholic steatohepatitis is characterized by inflammation and fibrosis, in addition to steatosis, of the liver, but no therapeutic agents have yet been established. The mast cell protease chymase can generate angiotensin II, matrix metalloproteinase-9 and transforming growth factor-β, all of which are associated with liver inflammation or fibrosis. In animal models of non-alcoholic steatohepatitis, augmented chymase has been observed in the liver. In histological analysis, chymase inhibitor prevented hepatic steatosis, inflammation and fibrosis. Chymase inhibitor also attenuated the augmentation of angiotensin II, matrix metalloproteinase-9 and transforming growth factor-β observed in the liver of non-alcoholic steatohepatitis. Oxidative stress, inflammatory markers, and collagen were attenuated by chymase inhibition. Moreover, chymase inhibitor showed a mitigating effect on established non-alcoholic steatohepatitis, and survival rates were significantly increased by treatment with chymase inhibitor. In this review, we propose that chymase inhibitor has potential as a novel therapy for NASH.

Keywords: chymase, non-alcoholic steatohepatitis, inhibitor, Inflammation, Fibrosis, Angiotensin II, matrix metalloproteinase-9, transforming growth factor-β

Received: 27 Sep 2017; Accepted: 09 Feb 2018.

Edited by:

Yuhei Nishimura, Mie University Graduate School of Medicine, Japan

Reviewed by:

Claudio Sorio, University of Verona, Italy
Cesario Bianchi, University of Mogi das Cruzes, Brazil
Tetsuo Nakata, Kyoto Pharmaceutical University, Japan  

Copyright: © 2018 Takai and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Shinji Takai, Osaka Medical College, Innovative Medicine, 2-7, Daigaku-machi, Takatsuki, 569-8686, Japan, pha010@art.osaka-med.ac.jp