Exosomal miR-320e through wnt2targeted inhibition of the Wnt/β-catenin pathway allevisate cerebral small vessel disease and cognitive impairment.
Exosomal miR-320e through wnt2targeted inhibition of the Wnt/β-catenin pathway allevisate cerebral small vessel disease and cognitive impairment.
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通过WNT2TARGETINGETS抑制Wnt/β-catenin途径的外泌体miR-320E减轻了脑小血管疾病和认知障碍。
DOI：
10.5498/wjp.v13.i9.630
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发表时间：
2023-09-19
影响因子：
3.1
通讯作者：
Ma AJ
中科院分区：
文献类型：
--
作者：
Wang Z;Li XN;Yang SN;Wang Y;Gao KJ;Han B;Ma AJ
外泌体 miRNA 在许多中枢神经系统疾病中发挥着至关重要的作用。脑小血管病（CVSD）是一种受多种因素影响的小血管疾病。本研究旨在探讨外泌体 miR-320e 在氧化应激刺激的 Wnt/β-catenin 通路中的作用，并评估其与 CVSD 患者精神症状的临床相关性。探讨外泌体 miR-320e 是否可以抑制 Wnt/β-catenin 通路并在 CVSD 进展中发挥保护作用，并检查其与 CVSD 患者认知障碍和抑郁症的潜在相关性。通过对 CVSD 患者和健康对照者的血浆外泌体进行测序，筛选出差异表达的外泌体 miRNA。使用生物信息学和双荧光素酶分析来确认 miR-320e 与 Wnt2 的结合，并评估在 H2O2 诱导的氧化应激下过表达或敲低 miR-320e 时 Wnt/β-catenin 通路下游成分的 mRNA 和蛋白质水平。此外，还使用靶向 Wnt2 的 siRNA 来证实 miR-320e 在 Wnt2 介导的 Wnt/β-catenin 通路抑制中的作用。对 CVSD 患者进行回顾性分析，以确认 miR-320e 表达与认知障碍和抑郁严重程度之间的相关性，分别使用蒙特利尔认知评估 (MoCA)/执行功能评估 (EFA) 和汉密尔顿抑郁量表 (HAMD)/贝克抑郁量表 (BDI) 进行量化。高通量测序显示，CVSD 患者的外泌体 miR-320e 下调。生物信息学分析和双荧光素酶报告基因实验表明，外泌体miR-320e通过靶向Wnt2的3'非编码区，抑制响应氧化应激的Wnt/β-catenin通路。将携带 miR-320e 的外泌体摄取到内皮细胞中也可以靶向 Wnt2 并抑制 Wnt2/β-catenin 通路。 miR-320e 表达升高可以保护 CVSD 患者免受相对严重的认知障碍和抑郁症的影响，因为它被发现与 MoCA/EFA 和 HAMD/BDI 评分呈正相关。我们的结果表明，外泌体 miR-320e 抑制 Wnt/β-catenin 通路，并可能在 CVSD 进展中发挥保护作用。
Exosomal miRNAs play crucial roles in many central nervous system diseases. Cerebral small vessel disease (CVSD) is a small vessel disease that is affected by various factors. This study aimed to investigate the role of exosomal miR-320e in the Wnt/β-catenin pathway stimulated by oxidative stress and assess its clinical correlation with psychiatric symptoms in patients with CVSD. To explore whether exosomal miR-320e could suppress the Wnt/β-catenin pathway and play a protective role in CVSD progression, as well as examine its potential correlation with cognitive impairment and depression in patients with CVSD. Differentially expressed exosomal miRNAs were filtered by sequencing plasma exosomes from patients with CVSD and healthy controls. Bioinformatics and dual luciferase analyses were used to confirm the binding of miR-320e to Wnt2, and the mRNA and protein levels of downstream components in the Wnt/β-catenin pathway were evaluated when overexpressed or with knockdown of miR-320e under H2O2-induced oxidative stress. In addition, Wnt2-targeting siRNA was used to confirm the role of miR-320e in the Wnt2-mediated inhibition of the Wnt/β-catenin pathway. A retrospective analysis was conducted among patients with CVSD to confirm the correlation between miR-320e expression and the severity of cognitive impairment and depression, which were quantified using the Montreal Cognitive Assessment (MoCA)/Executive Function Assessment (EFA), and the Hamilton Depression Scale (HAMD)/Beck Depression Inventory (BDI), respectively. High-throughput sequencing revealed that exosomal miR-320e was downregulated in patients with CVSD. Bioinformatics analysis and dual-luciferase reporter gene experiments showed that exosomal miR-320e inhibited the Wnt/β-catenin pathway in response to oxidative stress by targeting the 3' noncoding region of Wnt2. Uptake of exosomes carrying miR-320e into endothelial cells could also target Wnt2 and inhibit the Wnt2/β-catenin pathway. Elevated miR-320e expression may protect patients with CVSD from relatively severe cognitive impairment and depression, as it was found to have a positive correlation with the MoCA/EFA and HAMD/BDI scores. Our results suggest that exosomal miR-320e suppresses the Wnt/β-catenin pathway and may play a protective role in CVSD progression.
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DOI：
10.1038/nrneph.2016.54
发表时间：
2016-07
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Edeling M;Ragi G;Huang S;Pavenstädt H;Susztak K
通讯作者：
Susztak K
DOI：
10.1038/nrneurol.2017.188
发表时间：
2018-03
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Sweeney MD;Sagare AP;Zlokovic BV
通讯作者：
Zlokovic BV
影响因子：
8.3
作者：
Chen J;Chopp M
通讯作者：
Chopp M
影响因子：
5.5
作者：
Li H;Luo Y;Liu P;Liu P;Hua W;Zhang Y;Zhang L;Li Z;Xing P;Zhang Y;Hong B;Yang P;Liu J
通讯作者：
Liu J
外泌体：糖尿病血管并发症的生物标志物和治疗靶点
影响因子：
5.2
作者：
Chen A;Wang H;Su Y;Zhang C;Qiu Y;Zhou Y;Wan Y;Hu B;Li Y
通讯作者：
Li Y