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, Li, Song, Li‐Fang, Chen, Xiao‐Yi, Ma, Yan‐Li, Suo, Jun‐Fang, Shi, Jing‐He, and Chen, Guo‐Hong
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EPILEPSY ,ELECTRON-transfer catalysis ,KAINIC acid ,WESTERN immunoblotting ,MEMORY - Abstract
Summary: 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. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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