Department of Critical Care Medicine, Affiliated Hospital of Nantong University, Nantong, China.
Department of Electrocardiogram, Affiliated Hospital of Nantong University, Nantong, China.
Cell Biol Int. 2021 May;45(5):927-935. doi: 10.1002/cbin.11536. Epub 2021 Jan 7.
Acute lung injury (ALI) is a life-threatening medical condition with higher mortality and morbidity in elderly patients. Recently, metformin, a drug commonly used to lower blood glucose in type 2 diabetes patients, has been shown to be an effective anti-inflammatory agent in ALI. However, the mechanism of this regulation still remains poorly understood. In our study, we found that epithelial cell senescence was elevated after lipopolysaccharide (LPS) exposure in vivo and in vitro, accompanied by decreased expression of ATG5 and impaired autophagy activity. To further discover the molecular regulation mechanism between cellular senescence and autophagy in LPS-treated MLE-12 cells, we demonstrated that inhibition of ATG5 could decrease autophagy levels and promote the senescence of MLE-12 cells. On the contrary, elevating the expression of ATG5 could effectively suppress LPS-induced cellular senescence via enhancing autophagy activity. In addition, we demonstrated that metformin could protect MLE-12 cells from LPS-induced senescence via increasing the expression of ATG5 and augmenting autophagy activity. Our data implicate that activation of autophagy by metformin may provide a preventive and therapeutic strategy for ALI.
急性肺损伤（ALI）是一种危及生命的医学病症，老年患者的死亡率和发病率更高。最近，二甲双胍是一种常用于 2 型糖尿病患者降低血糖的药物，已被证明是 ALI 的一种有效抗炎剂。然而，这种调节的机制仍知之甚少。在我们的研究中，我们发现脂多糖（LPS）体内和体外暴露后上皮细胞衰老增加，同时 ATG5 表达降低，自噬活性受损。为了进一步发现 LPS 处理的 MLE-12 细胞中细胞衰老与自噬之间的分子调节机制，我们证明抑制 ATG5 可以降低自噬水平并促进 MLE-12 细胞衰老。相反，上调 ATG5 的表达可以通过增强自噬活性有效抑制 LPS 诱导的细胞衰老。此外，我们证明二甲双胍可以通过增加 ATG5 的表达和增强自噬活性来保护 MLE-12 细胞免受 LPS 诱导的衰老。我们的数据表明，二甲双胍通过激活自噬可能为 ALI 提供一种预防和治疗策略。
