Overexpression of long noncoding RNA Malat1 ameliorates traumatic brain injury induced brain edema by inhibiting AQP4 and the NF‐κB/IL‐6 pathway

Zhang, Yamin; Wang, Jianping; Zhang, Yi; Jia, Wei; Wu, Ruipeng; Cai, Hui

doi:10.1002/jcb.29025

Cited by 40 publications

(13 citation statements)

References 39 publications

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“…In addition to reducing mortality, heterozygosity for Rel del significantly rescued the shortened lifespan after TBI in both sexes and extended the lifespan of uninjured female flies ( Figure 5). Thus, similar to what has been observed in mammals, an attenuated but not absent NF-B-mediated injury response is sufficient to improve both acute and chronic outcomes of TBI in flies (Zhang et al 2019;Deng et al 2020;Long et al 2020).…”

Section: Rel Is a Dose-dependent Suppressor Of Tbi Outcomessupporting

confidence: 75%

Survival Following Traumatic Brain Injury in Drosophila Is Increased by Heterozygosity for a Mutation of the NF-κB Innate Immune Response Transcription Factor Relish

et al. 2020

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Traumatic brain injury (TBI) pathologies are caused by primary and secondary injuries. Primary injuries result from physical damage to the brain, and secondary injuries arise from cellular responses to primary injuries. A characteristic cellular response is sustained activation of inflammatory pathways commonly mediated by NF-κB transcription factors. Using a Drosophila melanogaster TBI model, we previously found that the main proximal transcriptional response to primary injuries is triggered by activation of Toll and Imd innate immune response pathways that engage NF-κB factors Dif and Relish (Rel), respectively. Here, we found by mass spectrometry that Rel protein level increased in fly heads at 4-8 h after TBI. To investigate the necessity of Rel for secondary injuries, we generated a null allele, Reldel, by CRISPR/Cas9 editing. When heterozygous but not homozygous, the Reldel mutation reduced mortality at 24 h after TBI and increased the lifespan of injured flies. Additionally, the effect of heterozygosity for Reldelon mortality was modulated by genetic background and diet. To identify genes that facilitate effects of Reldel on TBI outcomes, we compared genome-wide mRNA expression profiles of uninjured and injured +/+, +/Reldel, and Reldel/Reldel flies at 4 h following TBI. Only a few genes changed expression more than two-fold in +/Reldel flies relative to +/+ and Reldel/Reldel flies, and they were not canonical innate immune response genes. Therefore, Rel is necessary for TBI-induced secondary injuries but in complex ways involving Rel gene dose, genetic background, diet, and possibly small changes in expression of innate immune response genes.

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Section: Rel Is a Dose-dependent Suppressor Of Tbi Outcomessupporting

confidence: 75%

Survival Following Traumatic Brain Injury in Drosophila Is Increased by Heterozygosity for a Mutation of the NF-κB Innate Immune Response Transcription Factor Relish

et al. 2020

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“…Over-expressed MALAT1 abrogates astrocyte swelling through attenuating aquaporin 4 (AQP4), NF-κB, and IL-6 expressions in response to trauma. This study suggests the negative relationship between MALAT1 and TBI-related brain edema (Zhang et al, 2019d).…”

Section: Traumatic Brain Injurymentioning

confidence: 59%

“…It is reported that astrocyte swelling is one of the early consequences of TBI-induced brain edema. When astrocyte swelling occurs, the astrocyte volume is increased (Zhang et al, 2019d). MALAT1 expression is decreased in the edematous brain after TBI.…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

Long Non-coding RNAs and Circular RNAs: Insights Into Microglia and Astrocyte Mediated Neurological Diseases

Chen

Lai

Wang

et al. 2021

Front. Mol. Neurosci.

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Microglia and astrocytes maintain tissue homeostasis in the nervous system. Both microglia and astrocytes have pro-inflammatory phenotype and anti-inflammatory phenotype. Activated microglia and activated astrocytes can contribute to several neurological diseases. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), two groups of non-coding RNAs (ncRNAs), can function as competing endogenous RNAs (ceRNAs) to impair the microRNA (miRNA) inhibition on targeted messenger RNAs (mRNAs). LncRNAs and circRNAs are involved in various neurological disorders. In this review, we summarized that lncRNAs and circRNAs participate in microglia dysfunction, astrocyte dysfunction, neuron damage, and inflammation. Thereby, lncRNAs and circRNAs can positively or negatively regulate neurological diseases, including spinal cord injury (SCI), traumatic brain injury (TBI), ischemia-reperfusion injury (IRI), stroke, neuropathic pain, epilepsy, Parkinson’s disease (PD), multiple sclerosis (MS), and Alzheimer’s disease (AD). Besides, we also found a lncRNA/circRNA-miRNA-mRNA regulatory network in microglia and astrocyte mediated neurological diseases. Through this review, we hope to cast light on the regulatory mechanisms of lncRNAs and circRNAs in microglia and astrocyte mediated neurological diseases and provide new insights for neurological disease treatment.

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“…It has been reported that lncRNA plays an important role in stroke [6]. Zhang et al [19] found that upregulation of MALAT1 could protect brain injury by inhibiting AQP4. However, we found that the level of MALAT1 was upregulated after OGD-RX treatment for 24 and 48 h, which was consistent with the findings of Zhang et al [9] (Fig.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of LncRNA MALAT1 Attenuates Cerebral Ischemic Reperfusion Injury via Regulating AQP4 Expression

et al. 2020

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Stroke is one of the leading causes of mortality and disability worldwide. Long noncoding RNAs (lncRNAs) including MALAT1 have been shown to have critical roles in cerebral ischemia reperfusion injury (CIRI). However, the underlying mechanism of MALAT1 in CIRI has not been elucidated. The present study aimed to investigate the function and potential regulatory mechanism of MALAT1 in cerebral ischemic reperfusion injury. We established the middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation/reoxygenation (OGD/RX) model in vivo and in vitro, and then Cell Counting Kit-8 (CCK-8), RT-qPCR, flow cytometry analysis, lactate dehydrogenase (LDH) analysis, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to examine cell viability, MALAT1, aquaporin-4 (AQP4) expression, LDH release, and infarct volume, respectively. The level of AQP4 was remarkably upregulated in CIRI 24 h/48 h or OGD/RX 24 h/48 h compared with the sham group. Knockdown of AQP4 could alleviate OGD/RX-induced injury through enhancing cell viability and reducing LDH release and the rate of apoptotic cells. Furthermore, we found that MALAT1 was also increased in OGD/RX 24 h/48 h and silencing of MALAT1 could decrease AQP4. Inhibition of MALAT1 could also protect OGD/RX-induced injury, while the protective effect of MALAT1 siRNA on cerebral ischemic reperfusion was disappeared after transfection with AQP4 plasmid, indicating that MALAT1 may play a protective role in brain stroke through regulating AQP4. Taken together, our study provides evidence that MALAT1 is involved in ischemic stroke by inhibiting AQP4. Therefore, MALAT1 may serve as a potential target for therapeutic intervention in ischemic brain injury.

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Overexpression of long noncoding RNA Malat1 ameliorates traumatic brain injury induced brain edema by inhibiting AQP4 and the NF‐κB/IL‐6 pathway

Cited by 40 publications

References 39 publications

Survival Following Traumatic Brain Injury in Drosophila Is Increased by Heterozygosity for a Mutation of the NF-κB Innate Immune Response Transcription Factor Relish

Survival Following Traumatic Brain Injury in Drosophila Is Increased by Heterozygosity for a Mutation of the NF-κB Innate Immune Response Transcription Factor Relish

Long Non-coding RNAs and Circular RNAs: Insights Into Microglia and Astrocyte Mediated Neurological Diseases

Inhibition of LncRNA MALAT1 Attenuates Cerebral Ischemic Reperfusion Injury via Regulating AQP4 Expression

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