1. miR-21 alleviated apoptosis of cortical neurons through promoting PTEN-Akt signaling pathway in vitro after experimental traumatic brain injury.
- Author
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Han Z, Chen F, Ge X, Tan J, Lei P, and Zhang J
- Subjects
- Animals, Blotting, Western, Brain Injuries pathology, Cell Count, Cells, Cultured, Cerebral Cortex pathology, Fluorescent Antibody Technique, MicroRNAs genetics, Microtubule-Associated Proteins metabolism, Neurons pathology, PTEN Phosphohydrolase metabolism, Proto-Oncogene Proteins c-akt metabolism, Random Allocation, Rats, Wistar, Real-Time Polymerase Chain Reaction, Signal Transduction, Transfection, Apoptosis physiology, Brain Injuries physiopathology, Cerebral Cortex physiopathology, MicroRNAs metabolism, Neurons physiology
- Abstract
Traumatic brain injury (TBI) is a major cause of chronic disability and death in young adults worldwide. Multiple cellular, molecular and biochemical changes impact the development and outcome of TBI. Neuronal cell apoptosis, which is an important pathological change in secondary brain damage, is crucial to determine the functional recovery after TBI. miR-21, a widely-reported oncogene, which can reduce cell apoptosis in cancer, has been confirmed to be a pronounced up-regulated miRNA after TBI in animal model. Our study is designed to investigate whether miR-21 has the function of antiapoptosis in experimental TBI model in vitro and to explore the possible regulatory mechanism of miR-21 on neuronal apoptosis. The scratch cell injury was performed to mimic TBI-induced apoptosis in neurons, and miR-21 agomir/antagomir was transfected to up-/down-regulate the miR-21 level. Our data suggests that miR-21 can reduce the number of TUNEL-positive neurons. Meanwhile, miR-21 decreased the expression level of PTEN, and increased the phosphorylation of Akt significantly. In neurons transfected with miR-21 agomir, the expression of Bcl-2 was promoted while the caspase-3, caspase-9 and Bax level were down-regulated, which are crucially the downstream apoptosis-related proteins of PTEN-Akt signaling pathway. In conclusion, miR-21 can exert the function of reducing neuronal apoptosis through activating the PTEN-Akt signaling pathway. Our research provides new insights into the molecular mechanisms of neuronal apoptosis following TBI, which reminds that miR-21may be a potential therapeutic target for TBI treatment., (Copyright © 2014. Published by Elsevier B.V.)
- Published
- 2014
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