BMAL1 attenuates intracerebral hemorrhage-induced secondary brain injury in rats by regulating the Nrf2 signaling pathway

Gong, Yan; Zhang, Guoguo; Li, Bing; Cao, Cheng; Cao, Demao; Li, Xiang; Li, Haiying; Ye, Ming; Shen, Haitao; Chen, Gang

doi:10.21037/atm-21-1863

Cited by 15 publications

(12 citation statements)

References 63 publications

(85 reference statements)

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“…miRNAs have also been found to influence Nrf2. The miRNA-155 inhibitor antagomir-155 increases the expression of brain and muscle Arnt-like protein 1 (BMAL1) and activates the Nrf2 signaling pathway to attenuate neuroinflammation, oxidative stress, and neuronal death after ICH in rats ( 137 ). In addition, the miRNA-139/Nrf2/NF-κB axis may play a critical role in monomethyl fumarate’s (MF) role in conferring alleviation of neuroinflammation and oxidative stress, particularly considering that miR-139 overexpression reduces nuclear NF-κB levels and elevates nuclear Nrf2 levels in SH-SY5Y cells compared to controls and that levels of all three molecules are altered by MF treatment ( 138 ).…”

Section: Mechanism Of Microrna In Modulating Neuroinflammation After Ichmentioning

confidence: 99%

“…In addition, NF-κB also contributes significantly to the regulation of post-ICH neuroinflammation by miRNAs. The Nrf2 and PI3K/AKT pathways have been reported by several studies to be targeted by miRNAs, thus affecting the course of neuroinflammation after ICH ( 135 , 137 ). Of note, there are contradictory results concerning the effects of several miRNAs on their targets, such as miR-144 modulation of the mTOR autophagic pathway and of neurological functions ( 95 , 96 , 142 ).…”

Section: Prospects For New Therapiesmentioning

confidence: 99%

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MicroRNAs modulate neuroinflammation after intracerebral hemorrhage: Prospects for new therapy

Xia

Zheng²,

Feng³

et al. 2022

Front. Immunol.

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Intracerebral hemorrhage (ICH) is the most common subtype of hemorrhagic stroke. After ICH, blood components extravasate from vessels into the brain, activating immune cells and causing them to release a series of inflammatory mediators. Immune cells, together with inflammatory mediators, lead to neuroinflammation in the perihematomal region and the whole brain, and neuroinflammation is closely related to secondary brain injury as well as functional recovery of the brain. Despite recent progress in understanding the pathophysiology of ICH, there is still no effective treatment for this disease. MicroRNAs (miRNAs) are non-coding RNAs 17–25 nucleotides in length that are generated naturally in the human body. They bind complementarily to messenger RNAs and suppress translation, thus regulating gene expression at the post-transcriptional level. They have been found to regulate the pathophysiological process of ICH, particularly the neuroinflammatory cascade. Multiple preclinical studies have shown that manipulating the expression and activity of miRNAs can modulate immune cell activities, influence neuroinflammatory responses, and ultimately affect neurological functions after ICH. This implicates the potentially crucial roles of miRNAs in post-ICH neuroinflammation and indicates the possibility of applying miRNA-based therapeutics for this disease. Thus, this review aims to address the pathophysiological roles and molecular underpinnings of miRNAs in the regulation of neuroinflammation after ICH. With a more sophisticated understanding of ICH and miRNAs, it is possible to translate these findings into new pharmacological therapies for ICH.

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Section: Mechanism Of Microrna In Modulating Neuroinflammation After Ichmentioning

confidence: 99%

Section: Prospects For New Therapiesmentioning

confidence: 99%

MicroRNAs modulate neuroinflammation after intracerebral hemorrhage: Prospects for new therapy

Xia

Zheng²,

Feng³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

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“…Previous study show that Bmal1 directly regulates the Nrf2 signaling pathway by binding to its response element E-box ( Early et al, 2018 ). Recently, Gong et al (2021) found that miRNA-155 could negative regulate BMAL1 in mRNA level. Inhibiting miRNA-155 can promote the expression of BMAL1 and further activate the Nrf2 signaling pathway to attenuate brain injury induced by ICH.…”

Section: Regulation Of Nuclear Factor Erythroid-2-related Factor 2 Pa...mentioning

confidence: 99%

“…Brain and muscle Arnt-like protein 1 is a transcription factor and a principal driver of the molecular clock in mammals ( Gong et al, 2021 ). BMAL1 forms a heterodimer with CLOCK, which binds to E-box sites that have locations throughout the genome; this binding influences the rhythmic expression of various clock-controlled genes ( Early and Curtis, 2016 ).…”

Section: Regulation Of Nuclear Factor Erythroid-2-related Factor 2 Pa...mentioning

confidence: 99%

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Regulation of nuclear factor erythroid-2-related factor 2 as a potential therapeutic target in intracerebral hemorrhage

Zhang

Liu

et al. 2022

Front. Mol. Neurosci.

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Hemorrhagic stroke can be categorized into several subtypes. The most common is intracerebral hemorrhage (ICH), which exhibits significant morbidity and mortality, affecting the lives of millions of people worldwide every year. Brain injury after ICH includes the primary injury that results from direct compression as well as stimulation by the hematoma and secondary brain injury (SBI) that is due to ischemia and hypoxia in the penumbra around the hematoma. A number of recent studies have analyzed the mechanisms producing the oxidative stress and inflammation that develop following hematoma formation and are associated with the ICH induced by the SBI as well as the resulting neurological dysfunction. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a critical component in mediating oxidative stress and anti-inflammatory response. We summarize the pathological mechanisms of ICH focusing on oxidative stress and the regulatory role of Nrf2, and review the mechanisms regulating Nrf2 at the transcriptional and post-transcriptional levels by influencing gene expression levels, protein stability, subcellular localization, and synergistic effects with other transcription factors. We further reviewing the efficacy of several Nrf2 activators in the treatment of ICH in experimental ICH models. Activation of Nrf2 might produce antioxidant, anti-inflammatory, and neuron-protection effects, which could potentially be a focus for developing future treatments and prevention of ICH.

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miR-155-5p/Bmal1 Modulates the Senescence and Osteogenic Differentiation of Mouse BMSCs through the Hippo Signaling Pathway

Zhang,

Zheng

et al. 2023

Stem Cell Rev and Rep

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Background The core clock gene brain and muscle ARNT like-1 (Bmal1) is involved in the regulation of bone tissue aging. However, current studies are mostly limited to the establishment of the association between Bmal1 and bone senescence, without in-depth exploration of its main upstream and downstream regulatory mechanisms. Methods The luciferase reporter assay, RT-qPCR and Western blotting were performed to detect the interaction between miR-155-5p and Bmal1. The effects of miR-155-5p and Bmal1 on the aging and osteogenic differentiation ability of mouse bone marrow mesenchymal stem cells (BMSCs) were investigated by cell counting kit-8 (CCK-8) assay, flow cytometry, β-gal staining, alkaline phosphatase quantitative assay and alizarin red staining in vitro. The potential molecular mechanism was identified by ChIP-Seq, RNA-seq database analysis and immunofluorescence staining. Results The expression of Bmal1 declined with age, while the miR-155-5p was increased. miR-155-5p and Bmal1 repressed each other’s expression, and miR-155-5p targeted the Bmal1. Besides, miR-155-5p inhibited the proliferation and osteogenic differentiation of BMSCs, promoted cell apoptosis and senescence, inhibited the expression and nuclear translocation of YAP and TAZ. However, Bmal1 facilitated the osteogenic differentiation and suppressed the aging of BMSCs, meanwhile inactivated the Hippo pathway. Moreover, YAP inhibitors abrogated the positive regulation of aging and osteogenic differentiation in BMSCs by miR-155-5p and Bmal1. Conclusion In mouse BMSCs, miR-155-5p and Bmal1 regulated the aging and osteogenic differentiation ability of BMSCs mainly through the Hippo signaling pathway. Our findings provide new insights for the interventions in bone aging. Graphical Abstract

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BMAL1 attenuates intracerebral hemorrhage-induced secondary brain injury in rats by regulating the Nrf2 signaling pathway

Cited by 15 publications

References 63 publications

MicroRNAs modulate neuroinflammation after intracerebral hemorrhage: Prospects for new therapy

MicroRNAs modulate neuroinflammation after intracerebral hemorrhage: Prospects for new therapy

Regulation of nuclear factor erythroid-2-related factor 2 as a potential therapeutic target in intracerebral hemorrhage

miR-155-5p/Bmal1 Modulates the Senescence and Osteogenic Differentiation of Mouse BMSCs through the Hippo Signaling Pathway

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