Department of Physiology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea.
School of Pharmacy and Institute of New Drug Development, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea.
Biomolecules. 2021 Feb 8;11(2):242. doi: 10.3390/biom11020242.
Excess and sustained endoplasmic reticulum (ER) stress, paired with a failure of initial adaptive responses, acts as a critical trigger of nonalcoholic fatty liver disease (NAFLD) progression. Unfortunately, there is no drug currently approved for treatment, and the molecular basis of pathogenesis by ER stress remains poorly understood. Classical ER stress pathway molecules have distinct but inter-connected functions and complicated effects at each phase of the disease. Identification of the specific molecular signal mediators of the ER stress-mediated pathogenesis is, therefore, a crucial step in the development of new treatments. These signaling nodes may be specific to the cell type and/or the phase of disease progression. In this review, we highlight the recent advancements in knowledge concerning signaling nodes associated with ER stress and NAFLD progression in various types of liver cells.
过量且持续的内质网 (ER) 应激,加上初始适应性反应的失败,是导致非酒精性脂肪性肝病 (NAFLD) 进展的关键触发因素。不幸的是,目前尚无批准用于治疗的药物,并且 ER 应激发病机制的分子基础仍知之甚少。经典的 ER 应激途径分子在疾病的每个阶段都具有不同但相互关联的功能和复杂的影响。因此,确定 ER 应激介导的发病机制的特定分子信号介质是开发新治疗方法的关键步骤。这些信号节点可能特定于细胞类型和/或疾病进展阶段。在这篇综述中,我们强调了与 ER 应激和各种类型的肝细胞中 NAFLD 进展相关的信号节点的最新知识进展。