PDF(Pubmed)
Abstract：
Endoplasmic reticulum (ER) is the site for synthesis and folding of secreted and transmembrane proteins. Disturbance in the functioning of ER leads to the accumulation of unfolded and misfolded proteins, which finally activate the unfolded protein response (UPR) signaling. The three branches of UPR-IRE1 (Inositol requiring enzyme 1), PERK (Protein kinase RNA-activated (PKR)-like ER kinase), and ATF6 (Activating transcription factor 6)-modulate the gene expression pattern through increased expression of chaperones and restore ER homeostasis by enhancing ER protein folding capacity. The liver is a central organ which performs a variety of functions which help in maintaining the overall well-being of our body. The liver plays many roles in cellular physiology, blood homeostasis, and detoxification, and is the main site at which protein synthesis occurs. Disturbance in ER homeostasis is triggered by calcium level imbalance, change in redox status, viral infection, and so on. ER dysfunction and subsequent UPR signaling participate in various hepatic disorders like metabolic (dysfunction) associated fatty liver disease, liver cancer, viral hepatitis, and cholestasis. The exact role of ER stress and UPR signaling in various liver diseases is not fully understood and needs further investigation. Targeting UPR signaling with drugs is the subject of intensive research for therapeutic use in liver diseases. The present review summarizes the role of UPR signaling in liver disorders and describes why UPR regulators are promising therapeutic targets.
摘要：
内质网(ER)是分泌和跨膜蛋白合成和折叠的位点。内质网功能的紊乱导致未折叠和错误折叠蛋白质的积累，最终激活未折叠的蛋白质反应（UPR）信号。UPR-IRE1（肌醇需要酶1）的三个分支，PERK（蛋白激酶RNA激活（PKR）样ER激酶），和ATF6（激活转录因子6）通过增加伴侣的表达来调节基因表达模式，并通过增强ER蛋白折叠能力来恢复ER稳态。肝脏是一个中央器官，执行各种功能，有助于维持我们身体的整体健康。肝脏在细胞生理学中起着许多作用，血液稳态，和排毒,是蛋白质合成的主要部位。内质网稳态的紊乱是由钙水平失衡引发的，氧化还原状态的变化，病毒感染,等等。ER功能障碍和随后的UPR信号参与各种肝脏疾病，如代谢（功能障碍）相关的脂肪肝疾病，肝癌,病毒性肝炎,和胆汁淤积。ER应激和UPR信号在各种肝病中的确切作用尚不完全清楚，需要进一步研究。用药物靶向UPR信号传导是肝脏疾病治疗用途的深入研究的主题。本综述总结了UPR信号在肝脏疾病中的作用，并描述了为什么UPR调节剂是有希望的治疗靶标。
