1. MiR-181b inhibits P38/JNK signaling pathway to attenuate autophagy and apoptosis in juvenile rats with kainic acid-induced epilepsy via targeting TLR4.
- Author
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Wang L, Song LF, Chen XY, Ma YL, Suo JF, Shi JH, and Chen GH
- Subjects
- Animals, Disease Models, Animal, Epilepsy pathology, Female, Hippocampus metabolism, Hippocampus pathology, Kainic Acid, MAP Kinase Kinase 4 metabolism, Male, Neuroprotection physiology, Random Allocation, Rats, Wistar, p38 Mitogen-Activated Protein Kinases metabolism, Apoptosis physiology, Autophagy physiology, Epilepsy metabolism, MAP Kinase Signaling System physiology, MicroRNAs metabolism, Toll-Like Receptor 4 metabolism
- Abstract
Objective: To explore the role of miR-181b in alterations of apoptosis and autophagy in the kainic acid (KA)-induced epileptic juvenile rats via modulating TLR4 and P38/JNK signaling pathway., Methods: Dual-luciferase reporter assay was performed to testify the targeting relationship between miR-181b and TLR4. After intracerebroventricular injection (i.c.v.) of KA, rats were injected with miR-181b agomir and TLR4 inhibitor (TAK-242). The TLR-4 activator lipopolysaccharide (LPS) was also administered into rats immediately after injection with miR-181b agomir. Quantitative real-time-polymerase chain reaction (qRT-PCR) was used for detections of miR-181b and TLR4 expressions, hematoxylin-eosin (HE) and Nissl staining for observation of the hippocampus morphological changes, and TUNEL staining for apoptosis analysis. Moreover, western blot was determined to detect TLR4 and P38/JNK pathway proteins, as well as autophagy- and apoptosis-related proteins., Results: TLR4 was identified as a direct target of miR-181b using Dual-luciferase reporter assay. KA rats injected with miR-181b agomir or TAK-242 had improved learning and memory abilities, reduced seizure severity of Racine's scale, and lessened neuron injury. Additionally, miR-181b agomir or TAK-242 could significantly inhibit P38/JNK signaling, decrease LC3II/I, Beclin-1, ATG5, ATG7, ATG12, Bax, and cleaved caspases-3, but increase p62 and Bcl-2 expression. No significances were found between KA group and KA + miR-181b + LPS group., Conclusion: MiR-181b could inhibit P38/JNK signaling pathway via targeting TLR4, thereby exerting protective roles in attenuating autophagy and apoptosis of KA-induced epileptic juvenile rats., (© 2018 John Wiley & Sons Ltd.)
- Published
- 2019
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