Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
Aplicacions i Muntatge Torelló SL (AMT), 08570 Torelló, Spain.
Cells. 2021 Jun 7;10(6):1421. doi: 10.3390/cells10061421.
The pro-tumorigenic activity of fibroblast growth factor (FGF) 19 (FGF15 in its rodent orthologue) in hepatocellular carcinoma (HCC), as well as the unsolved problem that ischemia-reperfusion (IR) injury supposes in liver surgeries, are well known. However, it has been shown that FGF15 administration protects against liver damage and regenerative failure in liver transplantation (LT) from brain-dead donors without tumor signals, providing a benefit in avoiding IR injury. The protection provided by FGF15/19 is due to its anti-apoptotic and pro-regenerative properties, which make this molecule a potentially beneficial or harmful factor, depending on the disease. In the present review, we describe the preclinical models currently available to understand the signaling pathways responsible for the apparent controversial effects of FGF15/19 in the liver (to repair a damaged liver or to promote tumorigenesis). As well, we study the potential pharmacological use that has the activation or inhibition of FGF15/19 pathways depending on the disease to be treated. We also discuss whether FGF15/19 non-pro-tumorigenic variants, which have been developed for the treatment of liver diseases, might be promising approaches in the surgery of hepatic resections and LT using healthy livers and livers from extended-criteria donors.
成纤维细胞生长因子（FGF）19（其啮齿动物同源物为 FGF15）在肝细胞癌（HCC）中的促肿瘤活性，以及缺血再灌注（IR）损伤在肝外科手术中存在的未解决问题，都是众所周知的。然而，已经表明，FGF15 的给药可以防止没有肿瘤信号的脑死亡供体的肝移植（LT）中的肝损伤和再生失败，从而避免了 IR 损伤。FGF15/19 提供的保护归因于其抗凋亡和促再生特性，这使得这种分子成为一种潜在的有益或有害因素，具体取决于疾病。在本综述中，我们描述了目前可用的临床前模型，以了解负责 FGF15/19 在肝脏中明显有争议的作用的信号通路（修复受损的肝脏或促进肿瘤发生）。同样，我们研究了根据要治疗的疾病，激活或抑制 FGF15/19 途径的潜在药理学用途。我们还讨论了为治疗肝脏疾病而开发的 FGF15/19 非促肿瘤变异体是否可能是使用健康肝脏和扩展标准供体肝脏进行肝切除术和 LT 的有前途的方法。
