Plasma Exosomal miR-450b-5p as a Possible Biomarker and Therapeutic Target for Transient Ischaemic Attacks in Rats

Luo, Xiumei; Wang, Wei; Li, Dongbin; Xu, Chen; Liao, Bao; Li, FengMei; Zhou, Xia; Wu, Qin; Liu, Jingli

doi:10.1007/s12031-019-01341-9

Cited by 26 publications

(17 citation statements)

References 34 publications

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“…Inhibition of miR-450b-5p could attenuate hepatic IRI both in vivo and in vitro, notably. Consistent with our findings, a previous study has identified miR-450b-5p as a potential biomarker and therapy target in braintransient ischemic attacks 19 . Afterward, we selected out hypoxia for 6 h followed by 12-h reoxygenation for subsequent in vitro experiments on the basis of quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot results in RAW 264.7 cell line, a classic surrogate of Kupffer cell, regarding the dominant position of liver-resident macrophage upon progression of hepatic IRI-induced inflammation.…”

Section: Discussionsupporting

confidence: 93%

“…For the past few years, microRNAs have been testified to an essential regulator in pathology and physiology of liver 16,17 . miR-450b-5p was reported to be a latent biomarker in transient ischemic attack and liver selfhealing plasmodium malaria 18,19 . In our preliminary research, miR-450b-5p was significantly increased in cell hypoxia/reoxygenation (H/R) model, which is the classical in vitro model of hepatic IRI 20 .…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of miR-450b-5p ameliorates hepatic ischemia/reperfusion injury via targeting CRYAB

et al. 2020

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Hepatic ischemia/reperfusion injury (IRI) is an unavoidable course in liver transplantation, during which the immune response of inflammation plays a leading part. MicroRNA-450b-5p (miR-450b-5p), which has been reported to participate in several inflammatory diseases, was investigated in this study. The purpose of this study is to identify the potential function of miR-450b-5p toward remission of hepatic IRI and elucidate the specific mechanism. Herein we found that expression of miR-450b-5p, interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-6 was stimulated in hepatic IRI. Inhibition of miR-450b-5p could remarkably alleviate mouse hepatic IRI and improve liver function measured by hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), and enzyme-linked immunosorbent assay (ELISA). We further assessed protein expression undergoing Western blot and immunofluorescence, and discovered that miR-450b-5p suppressed alpha B-crystallin (CRYAB), thus restraining the inhibitory κB kinase (IKK) β-mediated canonical nuclear factor-κB (NF-κB) signaling, instead of the noncanonical path guided by IKKα in hepatic IRI. In addition, we demonstrated CRYAB as an activator of M2 polarization through protein kinase B (Akt) 1/mammalian target of rapamycin (mTOR), thus resulting in relief of liver IRI. Combination treatment containing both paths revealed a better antidamage efficacy than adjusting either path alone, suggesting that the joint therapy might be a promising solution in hepatic IRI.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Inhibition of miR-450b-5p ameliorates hepatic ischemia/reperfusion injury via targeting CRYAB

et al. 2020

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“…However, this situation has been greatly changed in the studies based on serum sEVs. The differential miRNAs identified in the present RNAseq study were well corroborated by these previous reports, such as the upregulation of hsa-miR-9 and hsa-miR-124 ( Ji et al, 2016 ), hsa-miR-223 ( Chen et al, 2017 ), and hsa-miR-450b-5p ( Luo et al, 2019 ), as well as the downregulation of miR-422a and miR-125b-2-3 ( Li D.B. et al, 2017 ).…”

Section: Discussionsupporting

confidence: 91%

Acute Cerebral Ischemia Increases a Set of Brain-Specific miRNAs in Serum Small Extracellular Vesicles

Zhou

Chao

et al. 2022

Front. Mol. Neurosci.

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Small extracellular vesicles (sEVs) miRNAs are promising diagnosis and prognosis biomarkers for ischemic stroke (IS). This study aimed to determine the impact of IS on the serum sEVs miRNA profile of IS patients and a transient middle cerebral artery occlusion (tMCAO) mouse model. Small RNAseq was used to define the serum sEVs miRNA profile in IS patients and healthy controls (HC), and tMCAO mice and sham controls. Among the 1,444 and 1,373 miRNAs identified in human and mouse serum sEVs, the expression of 424 and 37 miRNAs was significantly altered in the IS patients and tMCAO mice, respectively (| Log2FC| ≥ 1, p < 0.01). Notably, five of the top 25 upregulated miRNAs in IS patients were brain-specific or enriched, including hsa-miR-9-3p, hsa-miR-124-3p, hsa-miR-143-3p, hsa-miR-98-5p, and hsa-miR-93-5p. Upregulation of these four miRNAs was further validated by qPCR. Nine of the 20 upregulated miRNAs in tMCAO mice were also brain-specific or enriched miRNAs. Temporal analysis indicated that the dynamics of mmu-miR-9-5p, mmu-miR-124-3p, mmu-miR-129-5p, and mmu-miR-433-3p were closely correlated with the evolution of ischemic brain injury, as their expression increased at 0.5 days after the onset of ischemia, peaked at day 1 or 3, and returned to normal levels at day 7 and 14. Notably, with the exceptions of mmu-miR-128-3p, the expression of the other eight miRNAs in the mouse serum sEVs was unaffected in the lipopolysaccharide (LPS)-induced neuroinflammation model. Together, in this study, we provided a comprehensive view of the influences of IS on the serum sEVs miRNA profile of IS patients and tMCAO mice and demonstrated the increment of a set of brain-specific miRNAs in serum sEVs after acute cerebral ischemia, which could be promising candidates directly reflecting the ischemic brain injury.

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“…Almost all types of cells can secrete exosomes, which are widely distributed in body fluids, in which there are intracellular sources of lipids and RNA and other bioactive substances [ 15 ]. Exosomes can mediate intercellular communication, and it has been confirmed in recent studies that exosomes can participate in the remodeling process after cerebral infarction by mediating nucleotide and protein affecting angiogenesis and neuroglia [ 16 , 17 ]. At present, exosomes in the treatment of cerebral infarction is still limited to clinical research, mainly in stem cell expression of related genes and transport-related regulatory proteins.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Mesenchymal stem cell-derived exosome miR-542-3p suppresses inflammation and prevents cerebral infarction

Cai

Zhou

et al. 2021

Stem Cell Res Ther

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Background Cerebral infarction ranks as the second leading cause of disability and death globally, and inflammatory response of glial cells is the main cause of brain damage during cerebral infarction. Methods Studies have shown that mesenchymal stem cells (MSCs) can secrete exosomes and contribute to cerebral disease. Here, we would explore the function of MSC-derived exosome in cerebral infarction. Results Microarray indicated a decrease of miR-542-3p and an increase of Toll-Like Receptor 4 (TLR4) in middle cerebral artery occlusion (MCAO) mice comparing with sham mice. And luciferase and RIP analysis indicated a binding of miR-542-3p and TLR4. Then, we injected AAV9-miR-542-3p into paracele of sham or MCAO mice. Functional analysis showed that AAV9-miR-542-3p inhibited infarction area and the number of degenerating neurons and suppressed inflammatory factors’ expression and inflammatory cell infiltration. As well, transfection of miR-542-3p mimics into HA1800 cells underwent oxygen and glucose deprivation (OGD). Similarly, overexpression of miR-542-3p alleviated OGD induced cell apoptosis, ROS, and activation of inflammation response. Moreover, miR-542-3p could be packaged into MSCs and secreted into HA1800 cells. The extractive exosome-miR-21-3p treatment relieved MCAO- or OGD-induced cerebral injury and inflammation through targeting TLR4. Conclusion These results confirmed that MSC-derived exosome miR-542-3p prevented ischemia-induced glial cell inflammatory response via inhibiting TLR4. These results suggest possible therapeutic strategies for using exosome delivery of miR-542-3p to cure cerebral ischemic injury.

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Plasma Exosomal miR-450b-5p as a Possible Biomarker and Therapeutic Target for Transient Ischaemic Attacks in Rats

Cited by 26 publications

References 34 publications

Inhibition of miR-450b-5p ameliorates hepatic ischemia/reperfusion injury via targeting CRYAB

Inhibition of miR-450b-5p ameliorates hepatic ischemia/reperfusion injury via targeting CRYAB

Acute Cerebral Ischemia Increases a Set of Brain-Specific miRNAs in Serum Small Extracellular Vesicles

RETRACTED ARTICLE: Mesenchymal stem cell-derived exosome miR-542-3p suppresses inflammation and prevents cerebral infarction

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