Open Access

ARTICLE

The role of mTOR signaling pathway in regulating autophagy in liver injury of TX mice with Wilson’s disease

by Peng Wu^#, Manli Gao^#, Jianjian Dong, Chenchen Xu, Bo Li, Xun Wang, Yongzhu Han, Nan Cheng^*

Anhui University of Chinese Medicine, Hefei, 230038, China

* Address correspondence to: Nan Cheng,
# These authors contributed equally to this work

BIOCELL 2021, 45(1), 109-117. https://doi.org/10.32604/biocell.2021.012048

Received 12 June 2020; Accepted 15 September 2020; Issue published 26 January 2021

Abstract

Wilson disease (WD), known as hepatolenticular degeneration (HLD), is a treatable autosomal recessive disorder of copper metabolism. Because copper deposits in the liver first, the liver is not only the original defective organ but also the most affected organ. The liver injury is also one of the main causes of death throughout the course of the disease. Therefore, the treatment of liver injury is the main task of WD treatment, which is of great significance to improve the prognosis of patients. Autophagy is a process that promotes cell survival through degradation, recycling, and absorption in order to maintain the normal physiological function of cells, while excessive autophagy can aggravate cell death. In view of the abnormal damage of liver cells in patients with WD, which may be related to the change of autophagy level, in this study, we established an animal model of WD through toxic milk (TX) mice, observed the change of autophagy level in the liver, and observed the change of liver damage in mice after treatment with autophagy inhibitors. It was found that the mTOR signaling pathway was activated and autophagy was inhibited in Wilson mouse liver. After treatment with rapamycin, the autophagy level of mice liver was upregulated, and the copper content of mice liver was reduced, and the damage was alleviated. TX mouse hepatocytes were isolated, after using siRNA to interfere with mTOR expression, the copper accumulation was significantly reduced, which was the same with RAPA treatment. The results showed that in TX mice, the damage caused by copper accumulation in the liver may be related to the decrease of autophagy level caused by the activation of the mTOR signaling pathway. Our findings suggested that RAPA or the use of siRNA targeting mTOR may have potential applications in the treatment of Wilson’s disease.

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