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<p>Moyamoya disease (MMD) is a rare chronic progressive vascular anomaly of the skull base whose molecular regulatory mechanisms remain poorly understood. We therefore aimed to analyze the molecular mechanisms involved in the development of MMD from the perspective of miRNA regulation of mRNA. Raw gene expression profiles (GSE178501, GSE157628 and GSE189993) were downloaded from the Gene Expression Omnibus database and used to identify differentially expressed genes and perform functional enrichment analysis. Differentially expressed miRNAs and their predicted target genes were validated by RT-qPCR. Oxygen glucose deprivation was applied to induce an inflammatory injury cell model in human brain microvascular endothelial cells (BMEC). 973 differentially expressed mRNAs and 3 differentially expressed miRNAs were identified in three sets of gene expression profiles. RT-qPCR confirmed that the <i>miR-29b-3p</i> was upregulated in leukocytes of MMD and that the expression of <i>NTRK2</i> was downregulated. Dual-luciferase reporter assay indicated that <i>NTRK2</i> was the direct target of <i>miR-29b-3p</i>. Overexpression of <i>NTRK2</i> improved the viability of BMEC and increased the protein levels of NTRK2&#xa0;and pPI3K, while suppressed the expression of NLRP3, IL1β, and TNF-α. <i>miR-29b-3p</i> treatment partially abolished the protective effect of <i>NTRK2</i> and diminished the effect of NTRK2&#xa0;on PI3K/NLRP3 pathway. In conclusion, this study provided a novel insight into the pathophysiological mechanisms of MMD and demonstrated that the <i>miR-29b-3p</i>/<i>NTRK2</i>/PI3K/NLRP3 axis plays a pivotal role in the progression of MMD.</p>

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MicroRNA-29b-3p promotes endothelial cell inflammation via NTRK2/PI3K/NLRP3 pathway in Moyamoya disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月1日

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  • Liangzhe Wei,
  • He Ren,
  • Yuanwei Lin,
  • Xinpeng Deng,
  • Yuchun Liu,
  • Jingjing Zeng,
  • Jinghui Lin,
  • Xiang Gao,
  • Jie Sun,
  • Yi Huang

摘要

Moyamoya disease (MMD) is a rare chronic progressive vascular anomaly of the skull base whose molecular regulatory mechanisms remain poorly understood. We therefore aimed to analyze the molecular mechanisms involved in the development of MMD from the perspective of miRNA regulation of mRNA. Raw gene expression profiles (GSE178501, GSE157628 and GSE189993) were downloaded from the Gene Expression Omnibus database and used to identify differentially expressed genes and perform functional enrichment analysis. Differentially expressed miRNAs and their predicted target genes were validated by RT-qPCR. Oxygen glucose deprivation was applied to induce an inflammatory injury cell model in human brain microvascular endothelial cells (BMEC). 973 differentially expressed mRNAs and 3 differentially expressed miRNAs were identified in three sets of gene expression profiles. RT-qPCR confirmed that the miR-29b-3p was upregulated in leukocytes of MMD and that the expression of NTRK2 was downregulated. Dual-luciferase reporter assay indicated that NTRK2 was the direct target of miR-29b-3p. Overexpression of NTRK2 improved the viability of BMEC and increased the protein levels of NTRK2 and pPI3K, while suppressed the expression of NLRP3, IL1β, and TNF-α. miR-29b-3p treatment partially abolished the protective effect of NTRK2 and diminished the effect of NTRK2 on PI3K/NLRP3 pathway. In conclusion, this study provided a novel insight into the pathophysiological mechanisms of MMD and demonstrated that the miR-29b-3p/NTRK2/PI3K/NLRP3 axis plays a pivotal role in the progression of MMD.