Yi Zihan, Liu Jiahao, Shen Lanying, Hu Yue
Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
J Thorac Dis. 2025 Apr 30;17(4):2679-2692. doi: 10.21037/jtd-24-1817. Epub 2025 Apr 21.
Acute lung injury (ALI) poses a significant clinical challenge due to its high morbidity and mortality rates. Current treatment options are limited in their efficacy, necessitating the exploration of novel therapeutic targets. The mammalian target of rapamycin (mTOR), a crucial regulator of various cellular processes, has been implicated in the pathogenesis of ALI. Autophagy, a tightly regulated cellular degradation process controlled by mTOR, plays a pivotal role in the pathogenesis of ALI and cellular homeostasis. Mounting evidence also suggests that the mTOR pathway and autophagy play crucial roles in the pathogenesis and regulation of ALI. Herein, we reviewed the current understanding of how mTOR signaling and autophagy intersect in the context of ALI, with a focus on their roles across different cell types. This analysis highlights their dual roles in either promoting pulmonary injury or providing protection, depending on the specific cell types and different ALI models. Insights into the intricate balance between mTOR-mediated pathways and autophagic responses provide a foundation for developing targeted therapeutic strategies aimed at alleviating ALI through the modulation of these pathways. This review underscores the therapeutic potential of targeting mTOR and autophagy, presenting innovative and promising approaches for improving the clinical management and outcomes of ALI.
急性肺损伤(ALI)因其高发病率和死亡率而构成重大临床挑战。目前的治疗选择在疗效方面有限,因此需要探索新的治疗靶点。雷帕霉素的哺乳动物靶点(mTOR)是各种细胞过程的关键调节因子,已被认为与ALI的发病机制有关。自噬是一种受mTOR严格调控的细胞降解过程,在ALI的发病机制和细胞稳态中起关键作用。越来越多的证据还表明,mTOR途径和自噬在ALI的发病机制和调节中起关键作用。在此,我们综述了目前对mTOR信号传导和自噬在ALI背景下如何相互作用的理解,重点关注它们在不同细胞类型中的作用。该分析强调了它们在促进肺损伤或提供保护方面的双重作用,这取决于特定的细胞类型和不同的ALI模型。对mTOR介导的途径和自噬反应之间复杂平衡的深入了解为开发旨在通过调节这些途径来减轻ALI的靶向治疗策略奠定了基础。本综述强调了靶向mTOR和自噬的治疗潜力,为改善ALI的临床管理和预后提供了创新且有前景的方法。