Downregulation of miR-23a-3p improves cognitive function in rats after subarachnoid hemorrhage by targeting VCAN.

IF 1.2 4区医学 Q3 PATHOLOGY

Medical Molecular Morphology Pub Date : 2022-06-01 Epub Date: 2022-02-08 DOI:10.1007/s00795-022-00315-y

Cheng Xue, Rong Wang, Yu Jia

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引用次数: 0

Abstract

Subarachnoid hemorrhage (SAH) is a complicated and deadly disorder. Dysregulation of miRNAs in SAH has been widely reported. This investigation elucidated the function of miR-23a-3p in the in vivo and in vitro models of SAH. The miR-23a-3p and VCAN levels in SAH rats and sham controls were detected by RT-qPCR. The SAH rats were intracerebrally administrated with miR-23a-3p antagomir. Morphological changes and brain function were assessed. The isolated brain microvascular endothelial cells (BMECs), identified by immunofluorescence staining, were used as the model of SAH in vitro. The viability and apoptosis of BMECs were evaluated using MTT, flow cytometry, and western blotting analyses. Targeted relationship between miR-23a-3p and VCAN was predicted in miRDB and validated by a luciferase reporter assay. We found that the miR-23a-3p level was upregulated in rats after SAH, while VCAN was downregulated. Silencing miR-23a-3p attenuated neurological deficits and neuronal apoptosis in rats after SAH. VCAN was verified to be targeted by miR-23a-3p. Functionally, miR-23a-3p downregulation or VCAN overexpression inhibited BMEC apoptosis and promoted cell activity. Moreover, knockdown of VCAN eliminated the influence of miR-23a-3p inhibition in BMECs. Overall, suppression of miR-23a-3p improves cognitive function after SAH by targeting VCAN.

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下调miR-23a-3p靶向VCAN改善蛛网膜下腔出血大鼠认知功能。

蛛网膜下腔出血(SAH)是一种复杂而致命的疾病。SAH中mirna的失调已被广泛报道。这项研究阐明了miR-23a-3p在体内和体外SAH模型中的功能。RT-qPCR检测SAH大鼠和假对照组miR-23a-3p和VCAN水平。在SAH大鼠脑内给予miR-23a-3p拮抗剂。观察形态学变化及脑功能。采用免疫荧光法鉴定离体脑微血管内皮细胞(BMECs)作为体外SAH模型。采用MTT、流式细胞术和western blotting分析bmec细胞的生存能力和凋亡情况。miR-23a-3p和VCAN之间的靶向关系在miRDB中被预测，并通过荧光素酶报告基因试验得到验证。我们发现大鼠在SAH后miR-23a-3p水平上调，而VCAN水平下调。沉默miR-23a-3p可减轻SAH后大鼠的神经功能缺损和神经元凋亡。证实VCAN是miR-23a-3p的靶标。功能上，miR-23a-3p下调或VCAN过表达抑制BMEC凋亡，促进细胞活性。此外，VCAN的敲低消除了miR-23a-3p抑制在bmec中的影响。总体而言，抑制miR-23a-3p通过靶向VCAN改善SAH后的认知功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Medical Molecular Morphology 医学-病理学

CiteScore

2.90

自引率

5.60%

发文量

审稿时长

>12 weeks

期刊介绍： Medical Molecular Morphology is an international forum for researchers in both basic and clinical medicine to present and discuss new research on the structural mechanisms and the processes of health and disease at the molecular level. The structures of molecules, organelles, cells, tissues, and organs determine their normal function. Disease is thus best understood in terms of structural changes in these different levels of biological organization, especially in molecules and molecular interactions as well as the cellular localization of chemical components. Medical Molecular Morphology welcomes articles on basic or clinical research in the fields of cell biology, molecular biology, and medical, veterinary, and dental sciences using techniques for structural research such as electron microscopy, confocal laser scanning microscopy, enzyme histochemistry, immunohistochemistry, radioautography, X-ray microanalysis, and in situ hybridization. Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.