Melatonin Enhances the Therapeutic Effect of Plasma Exosomes Against Cerebral Ischemia-Induced Pyroptosis Through the TLR4/NF-κB Pathway

Wang, Kankai; Ru, Junnan; Zhang, Hengli; Chen, Jiayu; Lin, Xiao Yan; Lin, Zhongxiao; Wen, Ming‐Shien; Huang, Lijie; Ni, Haoqi; Zhuge, Qichuan; Yang, Shuxu

doi:10.3389/fnins.2020.00848

Cited by 70 publications

(47 citation statements)

References 74 publications

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“…For example, miR-184 can promote oligodendrocyte differentiation, control the proliferation and differentiation of adult neural stem/progenitor cells, and suppress glioma proliferation, migration, and invasion ( Liu et al, 2010 ; Cheng et al, 2015 ; Afrang et al, 2019 ), and suppression of miR-184 expression results in neuronal death after seizures in mice ( McKiernan et al, 2012 ). Our previous study demonstrated that miR-184 expression is significantly downregulated in the rat brain and in cultured cells following ischemia and reperfusion, which modulates post-OGD/R angiogenesis in vitro ( Wang et al, 2020 ). The results of the current study also revealed that downregulation of miR-184 expression contributes to neuronal cell damage and death in rats following ischemic stroke and induces SH-SY5Y cell apoptosis under OGD/R conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study found that miR-184 is among the top downregulated microRNAs in the blood of patients following ischemic stroke. The expression of miR-184 is significantly altered in the brain following ischemic stroke in rats ( Wang et al, 2020 ). MiR-184, a highly enriched microRNA in the mammalian brain, has been shown to promote oligodendrocyte differentiation and control the proliferation and differentiation of adult neural stem/progenitor cells ( Liu et al, 2010 ; Afrang et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats

Yang

Zhang

Chen

et al. 2021

Front. Mol. Neurosci.

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Our previous study revealed that miR-184 expression is significantly altered in the brain following ischemic stroke in rats. However, it is unknown whether this alteration in miR-184 expression contributes to brain injury after ischemic stroke. Here, we aim to address the potential of miR-184 to impact nerve injury following ischemia and reperfusion. Rats received ICV injection of miR-184 adenovirus or empty vector and were subjected to right middle cerebral artery occlusion (MCAO) to establish an ischemic stroke model. We cultured SH-SY5Y cells under oxygen-glucose deprivation/reoxygenation (OGD/R) and transfected them with miR-184 lentivirus to explore the primary mechanisms. To evaluate miR-184 expression, neurological function deficits, the cerebral infarct volume, cell viability, and apoptosis, qRT-PCR analysis of miR-184 expression, the modified neurological severity score (mNSS) system, TTC staining, the CCK-8 assay, flow cytometry, and dual-luciferase reporter assays were utilized. We found that miR-184 expression was downregulated and that the cerebral infarct volume and mNSSs were increased following ischemic stroke; however, increasing the level of miR-184 alleviated brain damage. Overexpression of miR-184 resulted in increased viability and reduced apoptosis of SH-SY5Y cells following OGD/R in vitro. We identified the phosphatidic acid phosphatase type 2B (PPAP2B) gene as a direct target gene of miR-184. In summary, our results reveal that attenuation of miR-184 levels in ischemic stroke contributes to ischemic injury through targeting PPAP2B mRNA-mediated apoptosis, which may be a promising therapeutic target for ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats

Yang

Zhang

Chen

et al. 2021

Front. Mol. Neurosci.

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“…In turn, melatonin combined with exosomes showed beneficial effects, like suppressing oxidative stress and apoptosis in vitro and inflammation, oxidative stress, DNA/mitochondrial damage, and apoptosis in vivo (45). Also, this therapeutic combination has exhibited an important protection of nervous system through the regulation of the TLR4/NF-kB signaling pathway (46). Also, exosome-melatonin therapy was found to mitigate vascular calcification and aging (47) and other beneficial therapeutic actions, that will be the scope of this review.…”

Section: Exosomes and Melatonin: Compatible Partnersmentioning

confidence: 96%

“…In this context, Wang et al (46) decided to investigate the therapeutic potential of plasma exosomes and melatonin in the damage to the nervous system caused by I/R. They treated rats with melatonin and isolated plasma exosomes using a model of focal cerebral ischemia.…”

Section: Exosome-melatonin Therapy Attenuates Vascular Calcification Ageing Ischemic Brain Injury and Neurodegenerative Diseasesmentioning

confidence: 99%

Exosomes and Melatonin: Where Their Destinies Intersect

et al. 2021

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Cell-to-cell communication is a broad and complex process associated with regular stimuli to maintain healthy cell interactions. One of the agents capable of cellular communication is known as an exosome, a subset of extracellular vesicles (EVs) released by the cell membrane. The exosome contains a wide range of functional proteins, mRNAs and miRNAs, which have the potential to interact with healthy or diseased cells in the body. On the other hand, melatonin also acts as a cellular communicator, produced and released by the pineal gland in a circadian way and also, non-circadian melatonin is derived from the mitochondria of all normal cells. In addition to exhibiting antioxidant, anti-inflammatory, anti-tumor and anti-aging activities, melatonin has recently been studied by its influence on exosomes. This review summarizes the relationship between exosomes and melatonin in various pathological processes. There is robust evidence that their combination ameliorates inflammation, ischemia-reperfusion injury, hepatic metabolic disturbance, cancer immunosuppression status, degenerative processes like chronic kidney disease, vascular calcification, ageing, ischemic brain injury, neurodegenerative diseases, obesity, colitis, wound healing and even embryonic development. Association of exosomes and melatonin represent a promising therapeutic tool, capable of interfering with basic molecular processes, such as oxidative stress and the inflammatory cascade, which support many pathophysiological aspects of diseases.

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“…A recent study reported by Wang et al (2020) injected blood-derived exosomes of melatonin-treated rats into the brain after focal cerebral ischemia. Melatonin changed the exosomal miRNAs profile and reduced ischemic changes via the promotion of angiogenesis, neurogenesis, and suppression of apoptosis.…”

Section: Effect Of Melatonin On Exosome Cargo Sortingmentioning

confidence: 99%

An Examination of the Putative Role of Melatonin in Exosome Biogenesis

Amini

Rezabakhsh

Heidarzadeh

et al. 2021

Front. Cell Dev. Biol.

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During the last two decades, melatonin has been found to have pleiotropic effects via different mechanisms on its target cells. Data are abundant for some aspects of the signaling pathways within cells while other casual mechanisms have not been adequately addressed. From an evolutionary perspective, eukaryotic cells are equipped with a set of interrelated endomembrane systems consisting of intracellular organelles and secretory vesicles. Of these, exosomes are touted as cargo-laden secretory vesicles that originate from the endosomal multivesicular machinery which participate in a mutual cross-talk at different cellular interfaces. It has been documented that cells transfer various biomolecules and genetic elements through exosomes to sites remote from the original cell in a paracrine manner. Findings related to the molecular mechanisms between melatonin and exosomal biogenesis and cargo sorting are the subject of the current review. The clarification of the interplay between melatonin and exosome biogenesis and cargo sorting at the molecular level will help to define a cell’s secretion capacity. This review precisely addresses the role and potential significance of melatonin in determining the efflux capacity of cells via the exosomal pathway. Certain cells, for example, stem cells actively increase exosome efflux in response to melatonin treatment which accelerates tissue regeneration after transplantation into the injured sites.

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Melatonin Enhances the Therapeutic Effect of Plasma Exosomes Against Cerebral Ischemia-Induced Pyroptosis Through the TLR4/NF-κB Pathway

Cited by 70 publications

References 74 publications

Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats

Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats

Exosomes and Melatonin: Where Their Destinies Intersect

An Examination of the Putative Role of Melatonin in Exosome Biogenesis

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