Programmed cell death and liver diseases

N. A. Onishchenko, Z. Z. Gonikova, A. Nikolskaya, L. A. Kirsanova, V. Sevastianov
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Abstract

Cell death represents the most critical pathologic entity in liver disease, which dictates pathologic consequences such as inflammation, fibrosis, and cell transformation. We analyzed the conclusions of studies on the involvement of different types of programmed cell death (PCD) in the pathogenesis of liver diseases. Three main forms of PCD (autophagy, apoptosis, necrosis) and five additional, still insufficiently studied PCD – necroptosis, ferroptosis, pyroptosis, partanatosis and entosis – observed in the liver in various acute and chronic diseases are considered. The involvement of several PCD at once in the development of any one pathology and one type of PCD in different pathologies was established. This indicates the existence of cross-regulation of metabolism in the liver cells with different levels of damage in the formation of the main dominant type of PCD. Available results indicate the possibility of attenuation (correction) of functional and morphological manifestations of PCD in the organ by controlled blocking of effector-mediated PCD pathways, as well as targeted induction of autophagy, anti-apoptotic and anti-necrotic mechanisms in liver cells.
程序性细胞死亡和肝脏疾病
细胞死亡是肝脏疾病中最重要的病理实体,它决定了诸如炎症、纤维化和细胞转化等病理后果。我们分析了不同类型的程序性细胞死亡(PCD)参与肝脏疾病发病机制的研究结论。三种主要形式的PCD(自噬,细胞凋亡,坏死)和另外五种尚未充分研究的PCD -坏死性下垂,铁下垂,焦下垂,partanatosis和内吞-在各种急性和慢性疾病的肝脏中观察到。在任何一种病理和一种不同病理的PCD类型的发展中,几个PCD同时参与是建立的。这表明不同损伤程度的肝细胞在主要优势型PCD的形成过程中存在代谢的交叉调节。现有的研究结果表明,通过有控制地阻断效应物介导的PCD通路,以及靶向诱导肝细胞自噬、抗凋亡和抗坏死机制,可能会减弱(纠正)器官中PCD的功能和形态表现。
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