MicroRNA-129-5p inhibits the development of autoimmune encephalomyelitis-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway

Liu, Aihua; Wu, Yougui; Wang, Yuping

doi:10.1016/j.brainresbull.2017.05.004

Cited by 75 publications

(50 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, several studies reported that miR-129-5p has a tumor-suppressive role by targeting HMBG1 in various human cancers [53,54]. Of note, Liu et al showed that miR-129-5p suppressed the progress of autoimmune encephalomyelitis (AE)-related epilepsy by inhibiting HMGB1/TLR4/NF-κB pathway [55]. In our study, HMBG1 was proved to be a target of miR-129-5p in BV-2 cells and its expression was increased in LPS treated BV-2 cells.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-129-5p alleviates spinal cord injury in mice via suppressing the apoptosis and inflammatory response through HMGB1/TLR4/NF-κB pathway

Wan

Tao

et al. 2020

Bioscience Reports

View full text Add to dashboard Cite

Secondary injury after spinal cord injury (SCI) is one reversible pathological change mainly involving excessive inflammatory response and neuro-apoptosis. Since in recent years, microRNAs (miRNAs) have been proposed as novel regulators of inflammation in different disease conditions. However, the role of miRNAs in the inflammatory response and apoptosis of secondary injury after SCI remains to be fully elucidated. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. The expression profiles of miRNA were examined using miRNA microarray, and among the candidate miRNAs, miR-129-5p was found to be the most down-regulated miRNA in spinal tissues. Overexpression of miR-129-5p using agomir-miR-129-5p promoted injury mice functional recovery, suppressed the apoptosis and alleviated inflammatory response in spinal tissues. Using LPS-induced BV-2 cell model, we found miR-129-5p was also proved in protecting inflammatory response and cell apoptosis in vitro. High-mobility group protein B1 (HMGB1), a well-known inflammatory mediator, was found to be directly targeted by miR-129-5p and it was associated with the inhibitory effect of miR-129-5p on the activation of toll-like receptor (TLR)-4 (TLR4)/ nuclear factor-κB (NF-κB) pathway in vitro and in vivo. Further experiments revealed that the anti-apoptosis and anti-inflammatory effects of miR-129-5p were reversed by HMGB1 overexpression in BV-2 cells. Collectively, these data revealed that miR-129-5p alleviated SCI in mice via suppressing the apoptosis and inflammatory response through HMGB1//TLR4/NF-κB pathway. Our data suggest that up-regulation of miR-129-5p may be a novel therapeutic target for SCI.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA-129-5p alleviates spinal cord injury in mice via suppressing the apoptosis and inflammatory response through HMGB1/TLR4/NF-κB pathway

Wan

Tao

et al. 2020

Bioscience Reports

View full text Add to dashboard Cite

show abstract

“…Inhibition of HMGB1 by MiRs‐129‐5p has been suggested from luciferase reporter gene assay (Liu et al . ). These results pave the way in utilizing single‐stranded RNAs that target HMGB1 which can provide a promising contribution in regards to the future treatment of epilepsy and related diseases.…”

Section: Hmgb1‐targeting Therapeutic Agents In Epilepsy: An Updatementioning

confidence: 97%

High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis: from pathogenesis to therapeutic approaches

Paudel

Semple

Jones

et al. 2019

Journal of Neurochemistry

View full text Add to dashboard Cite

Epilepsy is a serious neurological condition exhibiting complex pathology and deserving of more serious attention. More than 30% of people with epilepsy are not responsive to more than 20 anti‐epileptic drugs currently available, reflecting an unmet clinical need for novel therapeutic strategies. Not much is known about the pathogenesis of epilepsy, but evidence indicates that neuroinflammation might contribute to the onset and progression of epilepsy following acquired brain insults. However, the molecular mechanisms underlying these pathophysiological processes are yet to be fully understood. The emerging research suggests that high‐mobility group box protein 1 (HMGB1), a DNA‐binding protein that is both actively secreted by inflammatory cells and released by necrotic cells, might contribute to the pathogenesis of epilepsy. HMGB1 as an initiator and amplifier of neuroinflammation, and its activation is implicated in the propagation of seizures in animal models. The current review will highlight the potential role of HMGB1 in the pathogenesis of epilepsy, and implications of HMGB1‐targeted therapies against epilepsy. HMGB1 in this context is an emerging concept deserving further exploration. Increased understanding of HMGB1 in seizures and epilepsy will pave the way in designing novel and innovative therapeutic strategies that could modify the disease course or prevent its development.

show abstract

“…Targeting HMGB1/TLR4/RAGE signaling for epilepsy has gained more attention in recent years. MicroRNA-129-5p inhibited the development of autoimmune encephalomyelitis (AE)-related epilepsy by HMGB1 expression and inhibiting the TLR4/NF-κB signaling pathway ( Liu et al, 2017 ). HMGB1 and TLR4 antagonists slowed seizure precipitation, prevented acute and chronic seizure recurrence in C57BL/6 mice as well as reported increased expression of HMGB1 and TLR4 in human epileptogenic tissue, which is similar to a mouse model of chronic seizures and suggest a role for the HMGB1-TLR4 axis in human epilepsy ( Maroso et al, 2010 ).…”

Section: Role Of Hmgb1 In Epilepsymentioning

confidence: 99%

HMGB1: A Common Biomarker and Potential Target for TBI, Neuroinflammation, Epilepsy, and Cognitive Dysfunction

et al. 2018

View full text Add to dashboard Cite

High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein released by glia and neurons upon inflammasome activation and activates receptor for advanced glycation end products (RAGE) and toll-like receptor (TLR) 4 on the target cells. HMGB1/TLR4 axis is a key initiator of neuroinflammation. In recent days, more attention has been paid to HMGB1 due to its contribution in traumatic brain injury (TBI), neuroinflammatory conditions, epileptogenesis, and cognitive impairments and has emerged as a novel target for those conditions. Nevertheless, HMGB1 has not been portrayed as a common prognostic biomarker for these HMGB1 mediated pathologies. The current review discusses the contribution of HMGB1/TLR4/RAGE signaling in several brain injury, neuroinflammation mediated disorders, epileptogenesis and cognitive dysfunctions and in the light of available evidence, argued the possibilities of HMGB1 as a common viable biomarker of the above mentioned neurological dysfunctions. Furthermore, the review also addresses the result of preclinical studies focused on HMGB1 targeted therapy by the HMGB1 antagonist in several ranges of HMGB1 mediated conditions and noted an encouraging result. These findings suggest HMGB1 as a potential candidate to be a common biomarker of TBI, neuroinflammation, epileptogenesis, and cognitive dysfunctions which can be used for early prediction and progression of those neurological diseases. Future study should explore toward the translational implication of HMGB1 which can open the windows of opportunities for the development of innovative therapeutics that could prevent several associated HMGB1 mediated pathologies discussed herein.

show abstract

MicroRNA-129-5p inhibits the development of autoimmune encephalomyelitis-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway

Cited by 75 publications

References 42 publications

MicroRNA-129-5p alleviates spinal cord injury in mice via suppressing the apoptosis and inflammatory response through HMGB1/TLR4/NF-κB pathway

MicroRNA-129-5p alleviates spinal cord injury in mice via suppressing the apoptosis and inflammatory response through HMGB1/TLR4/NF-κB pathway

High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis: from pathogenesis to therapeutic approaches

HMGB1: A Common Biomarker and Potential Target for TBI, Neuroinflammation, Epilepsy, and Cognitive Dysfunction

Contact Info

Product

Resources

About