The Cellular, Molecular, and Pathologic Consequences of Stress on the Liver.
The Cellular, Molecular, and Pathologic Consequences of Stress on the Liver.
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压力对肝脏的细胞、分子和病理后果。
DOI：
10.1016/j.ajpath.2023.07.003
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Chakraborty,Sanjukta
中科院分区：
文献类型：
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作者：
Maiers,JessicaL;Chakraborty,Sanjukta
有充分证据表明，应激反应对肝组织有有害影响。应激和应激反应因素会破坏肝脏稳态并激活细胞和病理生理机制。 1 这反过来又会加剧急性和慢性肝脏病理状况。 2 尽管我们对这些机制的理解取得了重大进展，但在定义这些途径之间的串扰方面仍然存在重大差距。因此，在肝脏疾病的背景下，针对应激反应的治疗目标仍然具有挑战性。本期特刊是一系列评论，重点介绍导致肝病的压力和压力反应的不同类型和机制，以及如何有效管理这些相互关联的途径可能会发现新的治疗方案。应激反应途径，例如未折叠蛋白反应（UPR）、整合应激反应和氧化应激反应，在细胞适应病理状态并促进组织稳态恢复中发挥核心作用。 Hanquier 等人的综述 3 描述了 UPR 和综合应激反应在激活的肝星状细胞介导的肝纤维发生中的作用。多种应激反应机制汇聚在一起调节 UPR 和综合应激反应。因此，了解影响纤维发生的调控元件至关重要。本综述强调了针对活化的肝星状细胞和相关应激反应机制的治疗靶向对于减轻肝损伤和限制纤维化的重要性。越来越多的证据表明内质网应激与肝癌的进展有关。
It has been well documented that stress responses have detrimental effects on liver tissue. Stress and stress-responsive factors disrupt liver homeostasis and activate cellular and pathophysiological mechanisms. 1 This, in turn, exacerbates both acute and chronic hepatic pathologic conditions. 2 Although significant advances have been made in our understanding of these mechanisms, critical gaps remain in defining the crosstalk between these pathways. Consequently, therapeutic targeting of stress responses remains challenging in the context of liver diseases. This special theme issue is a collection of reviews that highlight the different types and mechanisms of stress and stress responses that contribute to liver disease and how effective management of these interconnected pathways may uncover novel treatment options. Stress response pathways, such as the unfolded protein response (UPR), the integrated stress response, and the oxidative stress response, play central roles in cellular adaptation of pathologic states and enable restoration of tissue homeostasis. The review by Hanquier et al 3 describes the role of UPR and integrated stress response in liver fibrogenesis mediated by activated hepatic stellate cells. Multiple stress-responsive mechanisms converge to regulate UPR and integrated stress response. Therefore, it is critical to understand the regulatory elements that impact fibrogenesis. This review highlights the importance of therapeutic targeting of activated hepatic stellate cells and associated stress response mechanisms to alleviate liver injury and limit fibrosis. Increasing evidence links endoplasmic reticulum stress with progression of liver cancers.