1. Metformin attenuates lipopolysaccharide-induced epithelial cell senescence by activating autophagy.
- Author
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Wang Y, Chen H, Sun C, Shen H, and Cui X
- Subjects
- Acute Lung Injury drug therapy, Acute Lung Injury metabolism, Animals, Autophagy physiology, Autophagy-Related Protein 5 antagonists & inhibitors, Autophagy-Related Protein 5 metabolism, Cell Line, Cellular Senescence physiology, Diabetes Mellitus, Type 2 metabolism, Disease Models, Animal, Epithelial Cells drug effects, Epithelial Cells metabolism, Lipopolysaccharides adverse effects, Lipopolysaccharides pharmacology, Lung metabolism, Male, Metformin metabolism, Mice, Mice, Inbred C57BL, Signal Transduction drug effects, Autophagy drug effects, Cellular Senescence drug effects, Metformin pharmacology
- Abstract
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., (© 2020 International Federation for Cell Biology.)
- Published
- 2021
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