Int J Med Sci 2019; 16(7):909-921. doi:10.7150/ijms.34245

Research Paper

Possible association of arrestin domain-containing protein 3 and progression of non-alcoholic fatty liver disease

Masahiro Ogawa#, Tatsuo Kanda#,✉, Teruhisa Higuchi, Hiroshi Takahashi, Tomohiro Kaneko, Naoki Matsumoto, Kazushige Nirei, Hiroaki Yamagami, Shunichi Matsuoka, Kazumichi Kuroda, Mitsuhiko Moriyama

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan
#These authors equally contributed.

Abstract

The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing worldwide. Several effective drugs for these diseases are now in development and under clinical trials. It is important to reveal the mechanism of the development of NAFLD and NASH. We investigated the role of arrestin domain-containing protein 3 (ARRDC3), which is linked to obesity in men and regulates body mass, adiposity and energy expenditure, in the progression of NAFLD and NASH. We performed knockdown of endogenous ARRDC3 in human hepatocytes and examined the inflammasome-associated gene expression by real-time PCR-based array. We also examined the effect of conditioned medium from endogenous ARRDC3-knockdown-hepatocytes on the apoptosis of hepatic stellate cells. We observed that free acids enhanced the expression of ARRDC3 in hepatocytes. Knockdown of ARRDC3 could lead to the inhibition of inflammasome-associated gene expression in hepatocytes. We also observed that conditioned medium from endogenous ARRDC3-knockdown-hepatocytes enhances the apoptosis of hepatic stellate cells. ARRDC3 has a role in the progression of NAFLD and NASH and is one of the targets for the development of the effective treatment of NAFLD and NASH.

Keywords: ARRDC3, Hepatic Stellate Cells, Inflammasome, NASH, Steatosis

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Ogawa M, Kanda T, Higuchi T, Takahashi H, Kaneko T, Matsumoto N, Nirei K, Yamagami H, Matsuoka S, Kuroda K, Moriyama M. Possible association of arrestin domain-containing protein 3 and progression of non-alcoholic fatty liver disease. Int J Med Sci 2019; 16(7):909-921. doi:10.7150/ijms.34245. Available from http://www.medsci.org/v16p0909.htm