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Hepatic stellate cell senescence in liver fibrosis: Characteristics, mechanisms and perspectives
Mechanisms of Ageing and Development ( IF 5.3 ) Pub Date : 2021-09-16 , DOI: 10.1016/j.mad.2021.111572
Mengfan Zhang 1 , Sandra Serna-Salas 1 , Turtushikh Damba 2 , Michaela Borghesan 3 , Marco Demaria 3 , Han Moshage 1
Affiliation  

Myofibroblasts play an important role in fibrogenesis. Hepatic stellate cells are the main precursors of myofibroblasts. Cellular senescence is the terminal cell fate in which proliferating cells undergo irreversible cell cycle arrest. Senescent hepatic stellate cells were identified in liver fibrosis. Senescent hepatic stellate cells display decreased collagen production and proliferation. Therefore, induction of senescence could be a protective mechanism against progression of liver fibrosis and the concept of therapy-induced senescence has been proposed to treat liver fibrosis. In this review, characteristics of senescent hepatic stellate cells and the essential signaling pathways involved in senescence are reviewed. Furthermore, the potential impact of senescent hepatic stellate cells on other liver cell types are discussed. Senescent cells are cleared by the immune system. The persistence of senescent cells can remodel the microenvironment and interact with inflammatory cells to induce aging-related dysfunction. Therefore, senolytics, a class of compounds that selectively induce death of senescent cells, were introduced as treatment to remove senescent cells and consequently decrease the disadvantageous effects of persisting senescent cells. The effects of senescent hepatic stellate cells in liver fibrosis need further investigation.



中文翻译:

肝纤维化中的肝星状细胞衰老:特征、机制和展望

肌成纤维细胞在纤维发生中起重要作用。肝星状细胞是肌成纤维细胞的主要前体细胞。细胞衰老是增殖细胞经历不可逆细胞周期停滞的终末细胞命运。在肝纤维化中鉴定出衰老的肝星状细胞。衰老的肝星状细胞显示胶原蛋白产生和增殖减少。因此,诱导衰老可能是一种防止肝纤维化进展的保护机制,并且已经提出治疗诱导衰老的概念来治疗肝纤维化。本综述综述了衰老肝星状细胞的特征以及与衰老相关的重要信号通路。此外,还讨论了衰老肝星状细胞对其他肝细胞类型的潜在影响。衰老细胞被免疫系统清除。衰老细胞的持续存在可以重塑微环境并与炎症细胞相互作用,从而诱导衰老相关功能障碍。因此,senolytics(一类选择性诱导衰老细胞死亡的化合物)被引入作为去除衰老细胞的处理方法,从而减少持续衰老细胞的不利影响。衰老肝星状细胞在肝纤维化中的作用有待进一步研究。被引入作为去除衰老细胞的处理方法,从而减少持续衰老细胞的不利影响。衰老肝星状细胞在肝纤维化中的作用有待进一步研究。被引入作为去除衰老细胞的处理方法,从而减少持续衰老细胞的不利影响。衰老肝星状细胞在肝纤维化中的作用有待进一步研究。

更新日期:2021-09-17
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