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通过增加矩阵金属蛋白酶3的表达,M6A修饰在脑缺血/再输损伤期间促进血脑屏障的破坏
En Liang1, Shaorong Xiao2, Changtong Zhao1
1Department of Neurosurgery, Guangzhou PanYu He Xian Memorial Hospital, Guangzhou, 511442, PR China.
Heliyon
|June 19, 2023
概括
N6-甲基氨酸 (m6A) 修饰通过增加矩阵金属蛋白酶-3 (MMP3) 表达,促进脑缺血-再输液 (I/R) 损伤中血脑屏障 (BBB) 的分解. 抑制m6A可能为I/R损伤提供治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 血脑屏障 (BBB) 的破坏在脑缺血-再输液 (I/R) 损伤中至关重要.
- 矩阵金属蛋白酶 (MMPs) 降解细胞外基质,导致BBB分解.
- N6-Methyladenosine (m6A) RNA修饰影响I/R损伤进展,但其在BBB分解和MMPs中的作用尚不清楚.
研究的目的:
- 为了研究m6A修改对脑I/R损伤中的BBB分解的影响.
- 阐明涉及MMPs表达的潜在机制.
- 探索m6A作为I/R损伤的潜在治疗点.
主要方法:
- 在小鼠中暂时的中脑动脉封闭和再输 (MCAO/R).
- 在小鼠大脑内皮细胞中缺氧-葡萄糖和再氧化 (OGD/R).
- 评估了MMP3表达,m6A修饰水平和BBB完整性.
主要成果:
- 在大脑I/R损伤中,MMP3表达及其m6A编写器CBLL1的水平升高.
- MMP3 mRNA 呈现了m6A 修饰,在 I/R 期间增加.
- 抑制m6A降低了MMP3表达,并改善了BBB分解.
结论:
- 通过增加MMP3表达,m6A修饰促进脑I/R损伤中的BBB分解.
- m6A代表了缓解大脑I/R损伤的潜在治疗标.
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