外体miR-30a-5p通过调节Notch1/VEGF信号通路来调节淋巴细胞内皮细胞的EndMT和血管生成
Yaxian Ning1, Xiaochun Zhou1, Gouqin Wang1
1Department of Nephrology, Second Hospital of Lanzhou University, Lanzhou 730030, Gansu, China.
Current gene therapy
|September 28, 2023
概括
异位体miR-30a-5p通过抑制内皮-介质细胞过渡 (EndMT) 和异常血管生成,防止糖尿病病 (DN). 这种微RNA可能为DN治疗提供一种新的治疗策略.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 糖尿病病 (DN) 是糖尿病的一种微血管并发症,其特征是内皮-介质细胞过渡 (EndMT) 和异常血管生成.
- 淋巴结膜内皮细胞 (GEC) 功能障碍在DN的发病过程中起着至关重要的作用.
研究的目的:
- 为了研究外体源微RNA-30a-5p (miR-30a-5p) 在高葡萄糖 (HG) 诱导的GEC功能障碍中的作用.
- 阐明潜在的分子机制,包括诺奇1/VEGF信号通路.
主要方法:
- GEC 暴露在正常或高葡萄糖条件下.
- 外体和miR-30a-5p模仿剂/抑制剂被用于治疗GEC;细胞增殖,迁移和细胞亡被评估.
- 用路西法酶试验,RT-qPCR和西式涂抹来分析基因和蛋白质表达.
- 在体内研究中,对DN小鼠进行了外体 miR-30a-5p 给药,以测量HbA1c和尿蛋白水平.
主要成果:
- 在HG治疗的GEC中,miR-30a-5p的表达下调.
- 外体miR-30a-5p增强了GEC的增殖和迁移,同时在HG条件下降低了细胞亡.
- miR-30a-5p直接针对Notch1,减少了Notch1和VEGF的表达.
- 异构体miR-30a-5p抑制了HG诱导的EndMT,并在DN小鼠中改善了功能标志物.
结论:
- 外体miR-30a-5p通过调节Notch1/VEGF通路来减轻GEC中的EndMT和异常血管生成.
- 外体miR-30a-5p显示出作为糖尿病病的治疗剂的潜力.
更多相关视频
07:49Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
11.3K
07:05TGF-β-mediated Endothelial to Mesenchymal Transition EndMT and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing
Published on: February 26, 2021
5.2K
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
Overview of Exosomes
2.7K
Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
2.7K
Mechanism of Angiogenesis
5.5K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.5K
Notch Signaling Pathway
4.3K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.3K
