RETRACTED ARTICLE: Exosomes-carried microRNA-26b-5p regulates microglia M1 polarization after cerebral ischemia/reperfusion

Li, Guangying; Xiao, Longhai; Qin, Hao; Zhuang, Qiang; Zhang, Weiwei; Liu, Long; Di, Chao; Zhang, Yabo

doi:10.1080/15384101.2020.1743912

Cited by 53 publications

(59 citation statements)

References 40 publications

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“…As the main immune cells resident in brain tissue, it has been proposed that microglia play an essential role in the progression of neuroinflammation (39). A recent study demonstrated that microglia acquired an M1 phenotype and secreted abundant pro-inflammatory cytokines during I/R injury (40). Immunofluorescence assay in this study showed that the microglia was activated in I/R injury induced cerebral pyroptosis.…”

Section: Discussionsupporting

confidence: 51%

Ablation of GSDMD Improves Outcome of Ischemic Stroke Through Blocking Canonical and Non-canonical Inflammasomes Dependent Pyroptosis in Microglia

Wang

Sun

et al. 2020

Front. Neurol.

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Ischemia/reperfusion (I/R) injury is a significant cause of mortality and long-term disability worldwide. Recent evidence has proved that pyroptosis, a novel cell death form, contributes to inflammation-induced neuron death and neurological function impairment following ischemic stroke. Gasdermin D (GSDMD) is a newly discovered key molecule of cell pyroptosis, but its biological function and precise role in ischemic stroke are still unclear. The present study investigates the cleavage activity of GSDMD, localization of pyroptotic cells, and global neuroinflammation in gsdmd−/− mice after I/R. The level of cell pyroptosis around the infarcted area was significantly increased in the acute phase of cerebral I/R injury. The ablation of GSDMD reduced the infraction volume and improved neurological function against cerebral I/R injury. Furthermore, we confirmed I/R injury induced cell pyroptosis mainly in microglia. Knockdown of GSDMD effectively inhibited the secretion of mature IL-1β and IL-18 from microglia cells but did not affect the expression of caspase-1/11 in vitro and in vivo. In summary, blocking GSDMD expression might serve as a potential therapeutic strategy for ischemic stroke.

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Section: Discussionsupporting

confidence: 51%

Ablation of GSDMD Improves Outcome of Ischemic Stroke Through Blocking Canonical and Non-canonical Inflammasomes Dependent Pyroptosis in Microglia

Wang

Sun

et al. 2020

Front. Neurol.

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“…Exosome-shuttled miR-92b-3p from ischemic preconditioned astrocytes protects neurons against oxygen and glucose deprivation (28). Exosomal miR-26a-5p level has been identi ed to be decreased in hUCMSCs, and exosomal miR-26b-5p from hUCMSCs could repress M1 polarization of microglia by targeting CH25H to inactivate the TLR pathway, then nally relieve nerve injury after cerebral I/R (29). In this study, we found that miR-26a-5p was downregulated in MSCs-derived exosomes of MCAO and OGD model.…”

Section: Discussionmentioning

confidence: 99%

MSCs‑derived exosomes attenuate ischemia-reperfusion brain injury and inhibit microglia apoptosis via exosomal miR-26a-5p mediated suppression of CDK6

Chang

Chen

Wang

et al. 2020

Preprint

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Background: This study aims to explore the role of mesenchymal stromal cells (MSCs)-derived exosomes (MSCs-Exo) in the cerebral ischemia-reperfusion (I/R) injury.Methods: Exosomes were isolated from MSCs of adult C57BL/6J mice by the gradient centrifugation method. The expression of miR-26a-5p and CDK6 in MSCs-Exo and mice brain tissues were evaluated by qRT-PCR and western blot. MiR-26a-5p mimics and miR-NC were transfected into MSCs, and exosomes were isolated from the stably expressing MSCs. Then MSCs-Exo-miR-26a-5p mimics or MSCs-Exo-miR-NC was injected into mice through the tail vein, or added into medium to stimulate BV-2 cells. Cell viability was evaluated by CCK-8 assay. Cell apoptosis was detected by flow cytometry. The apoptosis in brain tissues was evaluated by TUNEL staining assay. Bioinformatics analysis and luciferase reporter assay were performed to determine the relationship between miR-26a-5p and CDK6. Results: MiR-26a-5p was downregulated and CDK6 was upregulated in MSCs-Exo of MCAO and OGD model. MSCs-Exo-miR-26a-5p mimics significantly reduced cell apoptosis of OGD-injured BV-2 cells. MSCs-Exo-miR-26a-5p mimics significantly reduced infarct volume of MCAO-induced mice. Luciferase reporter assay revealed that CDK-6 was a target of miR-26a-5p. In addition, MSCs-Exo-miR-26a-5p mimics significantly decreased the expression of CDK6 in both OGD-induced BV-2 cells and MCAO-treated mice brains. Conclusion: Our results indicated that MSCs‑Exo attenuated I/R injury in mice by inhibiting microglia apoptosis via exosomal miR-26a-5p mediated suppression of CDK6. Our study shed light on the application of MSC-Exo as a potential therapeutic tool for cerebral I/R injury.

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“…In an established ischemia/reperfusion (I/R) rat model, exosomal mir‐26b‐5p inhibits M1 polarization of microglia via targeting CH25H and inactivating the TLR pathway, leading to reduced nerve injury after cerebral I/R. A reduction of exosomal mir‐26b‐5p has the opposite effect 71 . Recently, it was shown that expression levels of inflammatory cytokines elevate, whereas anti‐inflammatory cytokines (IL‐4, IL‐10) and mir‐30d‐5p decrease in AIS patients compared with normal control.…”

Section: Regulation Of the Nvu By Ncrnas In Ismentioning

confidence: 99%

Neurovascular Unit: A critical role in ischemic stroke

et al. 2021

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Ischemic stroke (IS), a common cerebrovascular disease, results from a sudden blockage of a blood vessel in the brain, thereby restricting blood supply to the area in question, and making a significantly negative impact on human health. Unfortunately, current treatments, that are mainly based on a recanalization of occluded blood vessels, are insufficient or inaccessible to many stroke patients. Recently, the profound influence of the neurovascular unit (NVU) on recanalization and the prognosis of IS have become better understood; in‐depth studies of the NVU have also provided novel approaches for IS treatment. In this article, we review the intimate connections between the changes in the NVU and IS outcomes, and discuss possible new management strategies having practical significance to IS. We discuss the concept of the NVU, as well as its roles in IS blood‐brain barrier regulation, cell preservation, inflammatory immune response, and neurovascular repair. Besides, we also summarize the influence of noncoding RNAs in NVU, and IS therapies targeting the NVU. We conclude that both the pathophysiological and neurovascular repair processes of IS are strongly associated with the homeostatic state of the NVU and that further research into therapies directed at the NVU could expand the range of treatments available for IS.

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RETRACTED ARTICLE: Exosomes-carried microRNA-26b-5p regulates microglia M1 polarization after cerebral ischemia/reperfusion

Cited by 53 publications

References 40 publications

Ablation of GSDMD Improves Outcome of Ischemic Stroke Through Blocking Canonical and Non-canonical Inflammasomes Dependent Pyroptosis in Microglia

Ablation of GSDMD Improves Outcome of Ischemic Stroke Through Blocking Canonical and Non-canonical Inflammasomes Dependent Pyroptosis in Microglia

MSCs‑derived exosomes attenuate ischemia-reperfusion brain injury and inhibit microglia apoptosis via exosomal miR-26a-5p mediated suppression of CDK6

Neurovascular Unit: A critical role in ischemic stroke

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