mir-330-5p from mesenchymal stem cell-derived exosomes targets SETD7 to reduce inflammation in rats with cerebral ischemia-reperfusion injury

IF 2.9 4区生物学 Q3 CELL BIOLOGY Journal of Molecular Histology Pub Date : 2024-12-31 DOI:10.1007/s10735-024-10347-6

WenTao Liu, YouJin Shen, RuiChun Pan, XiaoKun Qi

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Abstract

This study was to investigate the role of microRNA (miR)-330-5p derived from mesenchymal stem cells-secreted exosomes (MSCs-Exo) in cerebral ischemia-reperfusion injury (CI/RI) through targeting lysine N-methyltransferase SET domain containing 7 (SETD7). MSCs-Exo were separated and identified. MSCs-Exo were used to treat the middle cerebral artery occlusion (MCAO) rat model. By using the nerve injury score, Nissl, hematoxylin and eosin, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, the neural function, pathological alterations, and neuronal death in MCAO rats were examined. Using an enzyme-linked immunosorbent test, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in brain homogenate were tested. Rat brain expression levels of SETD7 and miR-330-5p were examined. Subsequently, the effects of MSCs-Exo, miR-330-5p, and SETD7 on neurological function and pathological alterations were assessed using gain and loss function tests. miR-330-5p expression was decreased and SETD7 expression was increased in the brain tissue of MCAO rats. Both MSCs-Exo and MSCs-Exo-derived miR-330-5p reduced inflammation in MCAO rats. miR-330-5p targeted SETD7, and SETD7 upregulation blocked the therapeutic effect of MSCs-Exo-derived miR-330-5p on MCAO rats. MSCs-Exo-derived miR-330-5p targets SETD7 to reduce inflammation in MCAO rats, providing a new therapeutic target for CI/RI therapy.

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来自间充质干细胞来源的外泌体的mir-330-5p靶向SETD7，以减少脑缺血再灌注损伤大鼠的炎症

本研究旨在通过靶向赖氨酸n -甲基转移酶SET结构域7 (SETD7)，探讨来自间充质干细胞分泌外泌体（MSCs-Exo）的microRNA (miR)-330-5p在脑缺血再灌注损伤（CI/RI）中的作用。对MSCs-Exo进行分离鉴定。采用MSCs-Exo治疗大鼠大脑中动脉闭塞（MCAO）模型。采用神经损伤评分法、尼氏染色法、苏木精染色法、伊红染色法及末端脱氧核苷酸转移酶dUTP镍端标记染色法观察MCAO大鼠神经功能、病理改变及神经元死亡情况。采用酶联免疫吸附试验检测脑匀浆中肿瘤坏死因子-α、白细胞介素(IL)-1β和IL-6的含量。检测大鼠脑内SETD7和miR-330-5p的表达水平。随后，通过增益和损失功能测试评估msc - exo、miR-330-5p和SETD7对神经功能和病理改变的影响。MCAO大鼠脑组织中miR-330-5p表达降低，SETD7表达升高。MSCs-Exo和MSCs-Exo衍生的miR-330-5p均可减轻MCAO大鼠的炎症。miR-330-5p靶向SETD7， SETD7上调阻断了msc - exo来源的miR-330-5p对MCAO大鼠的治疗作用。mscs - exo衍生的miR-330-5p靶向SETD7减轻MCAO大鼠的炎症，为CI/RI治疗提供了新的治疗靶点。

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来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.