Editorial
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2024; 30(18): 2391-2396
Published online May 14, 2024. doi: 10.3748/wjg.v30.i18.2391
Angiotensin-converting enzyme 2 and AMPK/mTOR pathway in the treatment of liver fibrosis: Should we consider further implications?
Michele Barone
Michele Barone, Section of Gastroenterology, Department of Precision and Regenerative Medicine - Jonian Area- University of Bari, Bari 70124, Italy
Author contributions: I declare that I conceived and wrote the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: Https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Michele Barone, MD, PhD, Associate Professor, Section of Gastroenterology, Department of Precision and Regenerative Medicine - Jonian Area- University of Bari, Piazza G Cesare 11, Bari 70124, Italy. michele.barone@uniba.it
Received: February 2, 2024
Revised: March 9, 2024
Accepted: April 17, 2024
Published online: May 14, 2024
Abstract

This editorial contains comments on the article by Zhao et al in print in the World Journal of Gastroenterology. The mechanisms responsible for hepatic fibrosis are also involved in cancerogenesis. Here, we recapitulated the complexity of the renin-angiotensin system, discussed the role of hepatic stellate cell (HSC) autophagy in liver fibrogenesis, and analyzed the possible implications in the development of hepatocarcinoma (HCC). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers definitively contribute to reducing hepatic fibrogenesis, whereas their involvement in HCC is more evident in experimental conditions than in human studies. Angiotensin-converting enzyme 2 (ACE2), and its product Angiotensin (Ang) 1-7, not only regulate HSC autophagy and liver fibrosis, but they also represent potential targets for unexplored applications in the field of HCC. Finally, ACE2 overexpression inhibits HSC autophagy through the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. In this case, Ang 1-7 acts binding to the MasR, and its agonists could modulate this pathway. However, since AMPK utilizes different targets to suppress the mTOR downstream complex mTOR complex 1 effectively, we still need to unravel the entire pathway to identify other potential targets for the therapy of fibrosis and liver cancer.

Keywords: Renin-angiotensin system, Liver fibrosis, Hepatic stellate cells, Autophagy, Hepatocellular carcinoma

Core Tip: In the light of clarifying the link between liver fibrosis and the development of hepatocellular carcinoma, we discussed the renin-angiotensin system involvement in liver fibrosis and hepatocarcinoma development, the specific mechanisms by which angiotensin-converting enzyme 2 (ACE2) regulates hepatic stellate cell (HSC) autophagy and consequently fibrosis, and the ACE2-dependent upstream signals modulating the AMP-activated protein kinase/mammalian target of the rapamycin pathway implicated in the regulation of HSC activation.