miR-21 alleviated apoptosis of cortical neurons through promoting PTEN-Akt signaling pathway in vitro after experimental traumatic brain injury

Han, Zhaoli; Chen, Fanglian; Ge, Xintong; Tan, Jin; Lei, Ping; Zhang, Jianning

doi:10.1016/j.brainres.2014.07.045

Cited by 104 publications

(66 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Then, we observed the impact of miR-21-5p on cellular apoptosis in rats and in-vitro cultured neurons to investigate the mechanism of its protective effect in TBI. We confirmed that miR-21 inhibited apoptosis in neurons through inhibiting PTEN expression at the post-transcriptional level and activating Akt signaling [18][19] . In addition, we evaluated the impact of miR-21-5p on BBB damage by measuring brain water content, the amount of Evan's Blue extravasation and the expression level of tight junction proteins in brain.…”

Section: Research Highlightsupporting

confidence: 69%

“…We have proved that neurons-expressed miR-21-5p exerted an anti-apoptosis effect in brain after TBI, thereby promoting the restoration of injured BBB and improving the neurological prognosis of TBI [15,[17][18][19] . Specifically, we employed the fluid percussion injury rat model, and detected the expression level of miR-21-5p in the traumatic focci using qRT-PCR.…”

Section: Research Highlightmentioning

confidence: 99%

See 1 more Smart Citation

miR-21, a potential therapeutic target of alleviating blood-brain barrier damage after traumatic brain injury

Lei

Zhang

2015

RNA Dis

View full text Add to dashboard Cite

Traumatic brain injury (TBI)is a disease with high morbidity and leads to high rate of disability and mortality. The blood-brain barrier (BBB) damage is an important pathological change in brain after TBI, which impacts the development and prognosis of the disease. In our previous research, we have reported that miR-21-5p in neurons can exert an anti-apoptosis effect, and promote the restoration of injured BBB after TBI. Up-regulation of miR-21-5p level in brain can amplify the above functions of miR-21-5p, thus alleviate BBB damage and improve the neurological prognosis of TBI. miR-21-3p, which is generated from pre-miR-21 at the same time with miR-21-5p, has been reported to play significant roles in regulating cellular apoptosis, immuno-inflammatory responses and the expression of angiogenic factors in various diseases. We made a summary of previous research on miR-21-3p and inferred that miR-21-3p could exert an important impact on BBB damage after TBI. Taken together, miR-21 is a vital miRNA that impacts the restoration of injured BBB, thus it could be a potential therapeutic target for interventions in TBI.

show abstract

Section: Research Highlightsupporting

confidence: 69%

Section: Research Highlightmentioning

confidence: 99%

miR-21, a potential therapeutic target of alleviating blood-brain barrier damage after traumatic brain injury

Lei

Zhang

2015

RNA Dis

View full text Add to dashboard Cite

show abstract

“…To investigate the function of miR-124-3p, miR-124-3p mimic (sequence: 59-UAAGGCACGCGGUGAAUGCCCA-39; GenePharma, Shanghai, China) was transfected into microglia as we described (27)(28)(29). In brief, the miR-21-3p mimic was diluted to a final concentration of 20 mM.…”

Section: Mir-124-3p Mimic Transfectionmentioning

confidence: 99%

“…As we reported (27,28), the mice were euthanized by cervical dislocation, and the neonatal brain was removed and fragmented in Dulbecco-Hanks' solution (Thermo Fisher Scientific). The meninges, blood vessels, and subcortical tissues were carefully stripped, and the cerebral cortex was minced into 1-mm 3 fragments.…”

Section: Primary Culture Of Cortical Neuronsmentioning

confidence: 99%

Increased miR‐124‐3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowthviatheir transfer into neurons

et al. 2017

Self Cite

View full text Add to dashboard Cite

Neuronal inflammation is the characteristic pathologic change of acute neurologic impairment and chronic traumatic encephalopathy after traumatic brain injury (TBI). Inhibiting the excessive inflammatory response is essential for improving the neurologic outcome. To clarify the regulatory mechanism of microglial exosomes on neuronal inflammation in TBI, we focused on studying the impact of microglial exosomal miRNAs on injured neurons in this research. We used a repetitive (r)TBI mouse model and harvested the injured brain extracts from the acute to the chronic phase of TBI to treat cultured BV2 microglia in vitro. The microglial exosomes were collected for miRNA microarray analysis, which showed that the expression level of miR-124-3p increased most apparently in the miRNAs. We found that miR-124-3p promoted the anti-inflamed M2 polarization in microglia, and microglial exosomal miR-124-3p inhibited neuronal inflammation in scratch-injured neurons. Further, the mammalian target of rapamycin (mTOR) signaling was implicated as being involved in the regulation of miR-124-3p by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Using the mTOR activator MHY1485 we confirmed that the inhibitory effect of exosomal miR-124-3p on neuronal inflammation was exerted by suppressing the activity of mTOR signaling. PDE4B was predicted to be the target gene of miR-124-3p by pathway analysis. We proved that it was directly targeted by miR-124-3p with a luciferase reporter assay. Using a PDE4B overexpressed lentivirus transfection system, we suggested that miR-124-3p suppressed the activity of mTOR signaling mainly through inhibiting the expression of PDE4B. In addition, exosomal miR-124-3p promoted neurite outgrowth after scratch injury, characterized by an increase on the number of neurite branches and total neurite length, and a decreased expression on RhoA and neurodegenerative proteins [Ab-peptide and p-Tau]. It also improved the neurologic outcome and inhibited neuroinflammation in mice with rTBI. Taken together, increased miR-124-3p in microglial exosomes after TBI can inhibit neuronal inflammation and contribute to neurite outgrowth via their transfer into neurons. miR-124-3p exerted these effects by targeting PDE4B, thus inhibiting the activity of mTOR signaling. Therefore, miR-124-3p could be a promising therapeutic target for interventions of neuronal inflammation after TBI. miRNAs manipulated microglial exosomes may provide a novel therapy for TBI and other neurologic diseases.-Huang, S., Ge, X., Yu, J., Han, Z., Yin, Z., Li, Y., Chen, F., Wang, H., Zhang, J., Lei, P. Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons. FASEB J. 32, 512-528 (2018). www.fasebj.org

show abstract

“…Consistent with this view of Akt as a key neuroprotective mechanism after CNS injury, others have shown that miR-21, which targets the Akt inhibitor PTEN, is neuroprotective after TBI. 42,43 Although the upregulation of miR-711 occurs rapidly after TBI, it persists for several days suggesting that the therapeutic window for intervention may be significant.…”

Section: Mir-711 Activates Neuronal Apoptosis B Sabirzhanov Et Almentioning

confidence: 99%

miR-711 upregulation induces neuronal cell death after traumatic brain injury

et al. 2015

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is a leading cause of mortality and disability. MicroRNAs (miRs) are small noncoding RNAs that negatively regulate gene expression at post-transcriptional level and may be key modulators of neuronal apoptosis, yet their role in secondary injury after TBI remains largely unexplored. Changes in miRs after controlled cortical impact (CCI) in mice were examined during the first 72 h using miR arrays and qPCR. One selected miR (711) was examined with regard to its regulation and relation to cell death; effects of miR-711 modulation were evaluated after CCI and using in vitro cell death models of primary cortical neurons. Levels of miR-711 were increased in the cortex early after TBI and in vitro models through rapid upregulation of miR-711 transcription (pri-miR-711) rather than catabolism. Increases coincided with downregulation of the pro-survival protein Akt, a predicted target of miR-711, with sequential activation of forkhead box O3 (FoxO3)a/glycogen synthase kinase 3 (GSK3)α/β, pro-apoptotic BH3-only molecules PUMA (Bcl2-binding component 3) and Bim (Bcl2-like 11 (apoptosis facilitator)), and mitochondrial release of cytochrome c and AIF. miR-711 and Akt (mRNA) co-immunoprecipitated with the RNA-induced silencing complex (RISC). A miR-711 hairpin inhibitor attenuated the apoptotic mechanisms and decreased neuronal death in an Aktdependent manner. Conversely, a miR-711 mimic enhanced neuronal apoptosis. Central administration of the miR-711 hairpin inhibitor after TBI increased Akt expression and attenuated apoptotic pathways. Treatment reduced cortical lesion volume, neuronal cell loss in cortex and hippocampus, and long-term neurological dysfunction. miR-711 changes contribute to neuronal cell death after TBI, in part by inhibiting Akt, and may serve as a novel therapeutic target.

show abstract

miR-21 alleviated apoptosis of cortical neurons through promoting PTEN-Akt signaling pathway in vitro after experimental traumatic brain injury

Cited by 104 publications

References 47 publications

miR-21, a potential therapeutic target of alleviating blood-brain barrier damage after traumatic brain injury

miR-21, a potential therapeutic target of alleviating blood-brain barrier damage after traumatic brain injury

Increased miR‐124‐3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowthviatheir transfer into neurons

miR-711 upregulation induces neuronal cell death after traumatic brain injury

Contact Info

Product

Resources

About