Stoess Christian, Choi Yeon-Kyung, Onyuru Janset, Friess Helmut, Hoffman Hal M, Hartmann Daniel, Feldstein Ariel E
Department of Pediatric Gastroenterology, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA.
Department of Surgery, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
Biomedicines. 2024 Mar 1;12(3):559. doi: 10.3390/biomedicines12030559.
Cell death is crucial for maintaining tissue balance and responding to diseases. However, under pathological conditions, the surge in dying cells results in an overwhelming presence of cell debris and the release of danger signals. In the liver, this gives rise to hepatic inflammation and hepatocellular cell death, which are key factors in various liver diseases caused by viruses, toxins, metabolic issues, or autoimmune factors. Both clinical and in vivo studies strongly affirm that hepatocyte death serves as a catalyst in the progression of liver disease. This advancement is characterized by successive stages of inflammation, fibrosis, and cirrhosis, culminating in a higher risk of tumor development. In this review, we explore pivotal forms of cell death, including apoptosis, pyroptosis, and necroptosis, examining their roles in both acute and chronic liver conditions, including liver cancer. Furthermore, we discuss the significance of cell death in liver surgery and ischemia-reperfusion injury. Our objective is to illuminate the molecular mechanisms governing cell death in liver diseases, as this understanding is crucial for identifying therapeutic opportunities aimed at modulating cell death pathways.
细胞死亡对于维持组织平衡和应对疾病至关重要。然而,在病理条件下,死亡细胞的激增会导致细胞碎片大量存在并释放危险信号。在肝脏中,这会引发肝脏炎症和肝细胞死亡,而这是由病毒、毒素、代谢问题或自身免疫因素引起的各种肝脏疾病的关键因素。临床和体内研究均有力地证实,肝细胞死亡是肝脏疾病进展的催化剂。这种进展的特征是炎症、纤维化和肝硬化的连续阶段,最终导致肿瘤发生风险增加。在本综述中,我们探讨细胞死亡的关键形式,包括凋亡、焦亡和坏死性凋亡,研究它们在急性和慢性肝脏疾病(包括肝癌)中的作用。此外,我们还讨论细胞死亡在肝脏手术和缺血再灌注损伤中的意义。我们的目标是阐明肝脏疾病中细胞死亡的分子机制,因为这种理解对于确定旨在调节细胞死亡途径的治疗机会至关重要。