《生命科学》 2021, 33(7): 876-887
内质网应激诱导的自噬在肝脏疾病中的研究进展
摘 要：
错误/ 未折叠蛋白的积累可导致内质网(endoplasmic reticulum, ER) 结构和功能紊乱，从而诱发内质网应激(endoplasmic reticulum stress, ERS)，激活未折叠蛋白反应(unfolded protein response, UPR)。UPR作为适应性机制可恢复早期的ERS，重建ER 稳态；当UPR 不足以缓解ERS 时，会通过UPR 介导的3 个跨膜蛋白(IRE1α、PERK、ATF6) 诱发细胞凋亡或自噬。自噬作为ERS 的另一种保护性反应，可通过降解错误折叠蛋白和清除受损细胞器来减轻ERS。另外，自噬是ERS 重要的下游事件并处于凋亡的上游，ERS介导的自噬可通过调节细胞凋亡发挥促凋亡或抗凋亡双重作用。ERS 与自噬间的相互作用在酒精/ 非酒精性脂肪肝、肝纤维化、肝癌等多种肝脏疾病中扮演着重要角色，但二者在肝病发生发展过程中的具体机制尚不明确。因此，探讨ERS 与自噬通过复杂的网络通路调控肝脏疾病的机制有助于改善相关肝脏疾病，这可能成为治疗肝病的有效靶点。
通讯作者：范 妤 , Email:806919125@qq.com
Abstract:
The accumulation of misfolded/unfolded proteins leads to the structural and functional disorder of the endoplasmic reticulum (ER), which induces endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). As an adaptive mechanism, UPR can reverse early ERS and restore ER homeostasis. When the UPR is insufficient to alleviate ERS, apoptosis or autophagy is induced by three UPR-mediated transmembrane proteins (IRE1α, PERK, and ATF6). Autophagy, as another protective response to ERS, can alleviate ERS by degrading misfolded proteins and clearing damaged organelles. In addition, autophagy is an important downstream event of ERS and is in the upstream of apoptosis. ERS-mediated autophagy plays a dual role of pro-apoptosis or antiapoptosis by regulating apoptosis. The interaction between ERS and autophagy plays an important role in a variety of liver diseases such as alcoholic/nonalcoholic fatty liver disease, liver fibrosis, and liver cancer, but the specific mechanism in the development and progression of liver disease is still unclear. Therefore, exploring the mechanisms of ERS and autophagy in regulating liver diseases through complex network pathways is helpful to improve related liver diseases, which may become an effective target for the treatment of liver diseases.
Communication Author：FAN Yu , Email:806919125@qq.com
