抑瘤素M通过抑制Mst1调控细胞自噬在高原缺氧中的研究进展

Research progress on the inhibition of Mst1-regulated autophagy by Oncostatin M under hypoxia at high altitude

摘要:

缺氧环境引发的细胞自噬是细胞适应低氧应激的重要机制，抑瘤素M（OSM）作为一种多功能细胞因子，近年来被发现参与调控缺氧条件下的自噬活动。哺乳动物Ste20样激酶1（Mst1）是调控自噬的关键节点，OSM通过抑制Mst1磷酸化，解除其对自噬相关蛋白Beclin-1的抑制作用，并影响YAP/TAZ-TEAD转录通路，从而促进自噬流，改善心肌细胞线粒体功能与存活。该文对高原缺氧环境下细胞损伤机制、自噬的基本功能及其保护作用进行阐述，旨在探究OSM通过调控细胞自噬过程改善细胞缺氧损伤及其与Mst1相关的分子机制，为高原缺氧损伤的治疗方法提供新思路。

Abstract:

Hypoxia-induced cellular autophagy is a crucial adaptive mechanism in response to low oxygen stress. Oncostatin M (OSM), a multifunctional cytokine, has recently been shown to modulate autophagy under hypoxic conditions. Mammalian Ste20-like kinase 1 (Mst1) is a key regulator of autophagy. OSM promotes autophagic flux by inhibiting Mst1 phosphorylation, which subsequently relieves the inhibitory effect of Mst1 on the autophagy-related protein Beclin-1 and influences the YAP/TAZ-TEAD transcriptional pathway. This process ultimately improves mitochondrial function and enhances the survival of cardiomyocytes. This review outlines the mechanisms of cellular injury in high-altitude hypoxic environments, the fundamental roles of autophagy, and its cytoprotective effects. It aims to explore the molecular mechanisms through which OSM alleviates hypoxic cell injury by regulating autophagy, particularly its relationship with Mst1, thereby providing new perspectives for the treatment of high-altitude hypoxic injury.