Yu Dian, Xie Yongpeng, Li Xiaomin
Department of Emergency and Critical Care Medicine, Lianyungang Hospital, Nanjing Medical University (Lianyungang First People's Hospital, School of Clinical Medicine, Nanjing Medical University), Lianyungang 222000, Jiangsu, China. Corresponding author: Li Xiaomin, Email:
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Aug;35(8):884-888. doi: 10.3760/cma.j.cn121430-20220705-00633.
The systemic inflammatory response caused by various pathogenic factors is a key stage in the development of acute respiratory distress syndrome (ARDS). At present, suppression of the inflammatory response and symptomatic support are main methods for the treatment of ARDS. Alveolar epithelial autophagy has an important role in the regulation of the inflammatory response in ARDS. Autophagy is a normal immune mechanism in the body, and it is a metabolic process by which phagocytes degrade intracellular components with the help of lysosomes to maintain intracellular homeostasis. Current studies have shown that pathogenic factors both inside and outside the lung can cause alveolar epithelial cells to form an unfavorable internal environment of hypoxia, starvation, infection, and even apoptosis by triggering inflammatory responses, leading to autophagy dysfunction. Excessive autophagy activation can continue to aggravate inflammatory responses. Autophagy related proteins such as Beclin1, microtubule-associated protein 1 light chain 3 (LC3), mammalian target of rapamycin (mTOR), and p62 are common autophagic markers in current research, which play a crucial role in regulating the autophagic process and the development of lung injury. Therefore, the expression of cellular autophagy genes can be used as early markers and important mechanisms of lung injury in septic ARDS. The Hippo signaling pathway is derived from the protein kinase Hippo in Drosophila, and the Hippo and autophagy are two conserved pathways that are essential for the protection of homeostasis in vivo. The mutual regulation of Hippo signaling pathway and autophagy is currently a hot topic in the academic community. This paper reviews the relevant literature to explore whether the Hippo signaling pathway can regulate cellular autophagy to alleviate the inflammatory response in septic ARDS, so as to provide further research directions for the treatment of ARDS.
由各种致病因素引起的全身炎症反应是急性呼吸窘迫综合征(ARDS)发展的关键阶段。目前,抑制炎症反应和对症支持是治疗ARDS的主要方法。肺泡上皮自噬在ARDS炎症反应调节中具有重要作用。自噬是机体正常的免疫机制,是吞噬细胞借助溶酶体降解细胞内成分以维持细胞内稳态的代谢过程。目前研究表明,肺内外致病因素均可通过触发炎症反应,使肺泡上皮细胞形成缺氧、饥饿、感染甚至凋亡的不良内环境,导致自噬功能障碍。过度的自噬激活会持续加重炎症反应。自噬相关蛋白如Beclin1、微管相关蛋白1轻链3(LC3)、哺乳动物雷帕霉素靶蛋白(mTOR)和p62是目前研究中常见的自噬标志物,它们在调节自噬过程及肺损伤发展中起关键作用。因此,细胞自噬基因的表达可作为脓毒症ARDS肺损伤早期标志物及重要机制。Hippo信号通路源于果蝇中的蛋白激酶Hippo,Hippo与自噬是体内维持稳态所必需的两条保守通路。Hippo信号通路与自噬的相互调控是目前学术界的研究热点。本文通过综述相关文献,探讨Hippo信号通路是否可调节细胞自噬以减轻脓毒症ARDS的炎症反应,为ARDS治疗提供进一步研究方向。