Lin28a attenuates cerebral ischemia/reperfusion injury through regulating Sirt3-induced autophagy.

Cerebral ischemia-reperfusion injury causes damage to local brain tissue and its function, but its specific pathogenesis is still unclear. Autophagy is an important catabolic pathway in eukaryotic cells, which is mainly used to remove damaged intracellular organelles, misfolded long-acting macromolecules and participate in cerebral ischemia-reperfusion injury. Lin28 is a highly conserved RNA-binding protein that plays a role in regulating gene translation, which is important for the growth and maintenance of pluripotent cells. Lin28a has been reported to have a clear protective effect on post-ischemic reperfusion injury of the heart. However, whether Lin28a has an effect on nerve injury after cerebral ischemia-reperfusion needs further study. In this study, we found that the expression of Lin28a was decreased in cerebral ischemia-reperfusion mice model. Upregulation of Lin28a could alleviate the nerve injury caused by ischemia-reperfusion, and promote autophagy of nerve cells. Upregulation of Lin28a reduced nerve cell apoptosis and relieved nerve cell injure induced by oxygen-glucose deprivation/reoxygenation. Lin28a increased the LC3-II levels in nerve cells, suggesting the promotion of autophagy. Mechanism studies indicated that Lin28a promoted autophagy mainly through regulating Sirt3 expression and activating AMPK-mTOR pathway. In conclusion, our study revealed the important role of Lin28a in cerebral ischemia-reperfusion and suggested that Lin28a was a protective factor for cerebral ischemia-induced injury.