Open Access
ARTICLE
The role of mTOR signaling pathway in regulating autophagy in liver injury of TX mice with Wilson’s disease
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.
Keywords
Cite This Article
WU, P., GAO, M., DONG, J., XU, C., LI, B. et al. (2021). The role of mTOR signaling pathway in regulating autophagy in liver injury of TX mice with Wilson’s disease.
BIOCELL, 45(1), 109–117. https://doi.org/10.32604/biocell.2021.012048
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