Section of Gastroenterology, Department of Precision and Regenerative Medicine - Jonian Area- University of Bari, Bari 70124, Italy.
World J Gastroenterol. 2024 May 14;30(18):2391-2396. doi: 10.3748/wjg.v30.i18.2391.
This editorial contains comments on the article by Zhao in print in the . 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.
这篇社论包含了对发表在 上的 Zhao 等人文章的评论。负责肝纤维化的机制也与癌症发生有关。在这里，我们重温了肾素-血管紧张素系统的复杂性，讨论了肝星状细胞 (HSC) 自噬在肝纤维化中的作用，并分析了其在肝癌 (HCC) 发展中的可能意义。血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂确实有助于减少肝纤维化，而它们在 HCC 中的作用在实验条件下比在人类研究中更为明显。血管紧张素转换酶 2 (ACE2) 及其产物血管紧张素 (Ang) 1-7 不仅调节 HSC 自噬和肝纤维化，而且它们也代表 HCC 领域未开发应用的潜在靶点。最后，ACE2 过表达通过 AMP 激活的蛋白激酶 (AMPK)/雷帕霉素靶蛋白 (mTOR) 途径抑制 HSC 自噬。在这种情况下，Ang 1-7 与 MasR 结合，其激动剂可以调节该途径。然而，由于 AMPK 利用不同的靶标有效地抑制 mTOR 下游复合物 mTOR 复合物 1，我们仍需要阐明整个途径，以确定纤维化和肝癌治疗的其他潜在靶点。
