Exosome-Encapsulated microRNA-140-5p Alleviates Neuronal Injury Following Subarachnoid Hemorrhage by Regulating IGFBP5-Mediated PI3K/AKT Signaling Pathway

Wang, Pinyan; Xue, Yanan; Zuo, Yuchun; Xue, Yinan; Zhang, Junyi; Duan, Jiajia; Liu, Fei; Liu, Aihua

doi:10.1007/s12035-022-03007-x

Cited by 18 publications

(11 citation statements)

References 38 publications

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“…In our previous study ( Lai et al, 2020 ), we used targeted delivery of modified Exo/miR-193-3p in brain tissue to alleviate neurobehavioral impairments and neuroinflammation following SAH. Wang et al (2022) found that exosome-encapsulated microR-140-5p could alleviate neuronal injury by regulating the IGFBP5-mediated PI3K/AKT signaling pathway in SAH. These studies provide broad prospects for the future treatment of SAH by regulating the tissue distribution or modification of circulating exosomal miRNAs for alleviating brain injury after SAH.…”

Section: Discussionmentioning

confidence: 94%

Diagnosis potential of subarachnoid hemorrhage using miRNA signatures isolated from plasma-derived extracellular vesicles

et al. 2023

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The diagnosis and clinical management of aneurysmal subarachnoid hemorrhage (aSAH) is currently limited by the lack of accessible molecular biomarkers that reflect the pathophysiology of disease. We used microRNAs (miRNAs) as diagnostics to characterize plasma extracellular vesicles in aSAH. It is unclear whether they can diagnose and manage aSAH. Next-generation sequencing (NGS) was used to detect the miRNA profile of plasma extracellular vesicles (exosomes) in three patients with SAH and three healthy controls (HCs). We identified four differentially expressed miRNAs and validated the results using quantitative real-time polymerase chain reaction (RT-qPCR) with 113 aSAH patients, 40 HCs, 20 SAH model mice, and 20 sham mice. Exosomal miRNA NGS revealed that six circulating exosomal miRNAs were differentially expressed in patients with aSAH versus HCs and that the levels of four miRNAs (miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p) were differentially significant. After multivariate logistic regression analysis, only miR-369-3p, miR-486-3p, and miR-193b-3p enabled prediction of neurological outcomes. In a mouse model of SAH, greater expression of miR-193b-3p and miR-486-3p remained statistically significant relative to controls, whereas expression levels of miR-369-3p and miR-410-3p were lower. miRNA gene target prediction showed six genes associated with all four of these differentially expressed miRNAs. The circulating exosomes miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p may influence intercellular communication and have potential clinical utility as prognostic biomarkers for aSAH patients.

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Section: Discussionmentioning

confidence: 94%

Diagnosis potential of subarachnoid hemorrhage using miRNA signatures isolated from plasma-derived extracellular vesicles

et al. 2023

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“…A concise review of the existing literature regarding the role of these three miRNAs in AIS is presented in Table 2 . In animal models simulating ischemic stroke, a significant decrease in miR-140–5p expression was observed within the ischemic core ( 27 – 29 ). Conversely, when examining human serum samples, all studies consistently reported an elevation in serum miR-140–5p levels after cerebral ischemia ( 30 – 32 ).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, studies have also explored the therapeutic potential of miR-140–5p. Wang et al demonstrated that administration of encapsulated miR-140–5p could alleviate neuronal damage in subarachnoid hemorrhage( 27 ). Liang et al’s work showcased that overexpressing miR-140–5p using adeno-associated viruses reduced inflammatory and vascular growth factors in the ischemic mouse hippocampus, inhibiting neurogenesis and capillary density( 30 ).…”

Section: Resultsmentioning

confidence: 99%

MicroRNA Expression Profile in Acute Ischemic Stroke

Mainali,

Nepal,

Webb

et al. 2024

Preprint

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Introduction: Acute ischemic stroke with large vessel occlusion (LVO) continues to present a considerable challenge to global health, marked by substantial morbidity and mortality rates. Although definitive diagnostic markers exist in the form of neuroimaging, their expense, limited availability, and potential for diagnostic delay can often result in missed opportunities for life-saving interventions. Despite several past attempts, research efforts to date have been fraught with challenges likely due to multiple factors such as inclusion of diverse stroke types, variable onset intervals, differing pathobiologies, and a range of infarct sizes, all contributing to inconsistent circulating biomarker levels. In this context, microRNAs (miRNAs) have emerged as a promising biomarker, demonstrating potential as biomarkers across various diseases, including cancer, cardiovascular conditions, and neurological disorders. These circulating miRNAs embody a wide spectrum of pathophysiological processes, encompassing cell death, inflammation, angiogenesis, neuroprotection, brain plasticity, and blood-brain barrier integrity. This pilot study explores the utility of circulating exosome-enriched extracellular vesicle (EV) miRNAs as potential biomarkers for anterior circulation LVO (acLVO) stroke.Methods: In our longitudinal prospective cohort study, we collected data from acute large vessel occlusion (acLVO) stroke patients at four critical time intervals post-symptom onset: 0–6 hours, 6–12 hours, 12–24 hours, and 5–7 days. For comparative analysis, healthy individuals were included as control subjects. In this study, extracellular vesicles (EVs) were isolated from the plasma of participants, and the miRNAs within these EVs were profiled utilizing the NanoString nCounter system. Complementing this, a scoping review was conducted to examine the roles of specific miRNAs such as miR-140-5p, miR-210-3p, and miR-7-5p in acute ischemic stroke (AIS). This review involved a targeted PubMed search to assess their influence on crucial pathophysiological pathways in AIS, and their potential applications in diagnosis, treatment, and prognosis. The review also included an assessment of additional miRNAs linked to stroke.Results: Within the first 6 hours of symptom onset, three specific miRNAs (miR-7-5p, miR-140-5p, and miR-210-3p) exhibited significant differential expression compared to other time points and healthy controls. These miRNAs have previously been associated with neuroprotection, cellular stress responses, and tissue damage, suggesting their potential as early markers of acute ischemic stroke.Conclusion: This study highlights the potential of circulating miRNAs as blood-based biomarkers for hyperacute acLVO ischemic stroke. However, further validation in a larger, risk-matched cohort is required. Additionally, investigations are needed to assess the prognostic relevance of these miRNAs by linking their expression profiles with radiological and functional outcomes.

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“…In another rat model of ICH, MSC exosome-transferred miR-133b (100 μg via the tail vein, i.v., 72 h after ICH) reduced neuronal apoptosis and neurodegeneration by RhoA downregulation and ERK1/2/CREB pathway activation [ 58 ]. A recent report by Wang and colleagues showed that ADSC-Exos could decline neurological deficits and promote cell viability through suppression of insulin-like growth factor-binding protein 5 (IGFBP5) and increase in the expression of PI3K/Akt signaling pathway components in in vitro and in vivo models of SAH [ 59 ]. Recent studies have shown that BDNF could confer protection against apoptosis and neuronal injury by activating the ERK and/or PI3K/Akt pathway to stimulate the phosphorylation of CREB [ 76 , 77 ].…”

Section: Neurodegenerative Diseases Neurological Disorders and Exosom...mentioning

confidence: 99%

The Exosome-Mediated PI3K/Akt/mTOR Signaling Pathway in Neurological Diseases

Iranpanah

Moradi

Saso³

et al. 2023

Pharmaceutics

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As major public health concerns associated with a rapidly growing aging population, neurodegenerative diseases (NDDs) and neurological diseases are important causes of disability and mortality. Neurological diseases affect millions of people worldwide. Recent studies have indicated that apoptosis, inflammation, and oxidative stress are the main players of NDDs and have critical roles in neurodegenerative processes. During the aforementioned inflammatory/apoptotic/oxidative stress procedures, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a crucial role. Considering the functional and structural aspects of the blood–brain barrier, drug delivery to the central nervous system is relatively challenging. Exosomes are nanoscale membrane-bound carriers that can be secreted by cells and carry several cargoes, including proteins, nucleic acids, lipids, and metabolites. Exosomes significantly take part in the intercellular communications due to their specific features including low immunogenicity, flexibility, and great tissue/cell penetration capabilities. Due to their ability to cross the blood–brain barrier, these nano-sized structures have been introduced as proper vehicles for central nervous system drug delivery by multiple studies. In the present systematic review, we highlight the potential therapeutic effects of exosomes in the context of NDDs and neurological diseases by targeting the PI3K/Akt/mTOR signaling pathway.

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Exosome-Encapsulated microRNA-140-5p Alleviates Neuronal Injury Following Subarachnoid Hemorrhage by Regulating IGFBP5-Mediated PI3K/AKT Signaling Pathway

Cited by 18 publications

References 38 publications

Diagnosis potential of subarachnoid hemorrhage using miRNA signatures isolated from plasma-derived extracellular vesicles

Diagnosis potential of subarachnoid hemorrhage using miRNA signatures isolated from plasma-derived extracellular vesicles

MicroRNA Expression Profile in Acute Ischemic Stroke

The Exosome-Mediated PI3K/Akt/mTOR Signaling Pathway in Neurological Diseases

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