低氧驱动的组素修饰景观和EZH2在视网膜新血管化中的作用
Yong Lin1, Rusen Yang1, Tianyi Xu1
1State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Experimental eye research
|September 28, 2025
概括
增强肠胃同源2 (EZH2) 驱动视网膜新血管化 (RNV) 通过抑制针对KDR.的miR-221. 抑制EZH2降低了RNV,这表明EZH2是RNV疾病的潜在治疗标.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 眼科医生 眼科 眼科
背景情况:
- 增强体质同类物2 (EZH2) 是一种调节关键细胞过程的基因组甲基转移酶.
- EZH2在视网膜新血管化 (RNV) 中的作用尚不清楚.
- 缺氧是RNV的已知触发因素,并且影响着组蛋白修饰.
研究的目的:
- 为了研究EZH2-介导的H3K27三甲基化在人类视网膜微血管内皮细胞 (HRMECs) 在缺氧下的作用.
- 阐明将EZH2与RNV联系起来的分子机制.
- 评估EZH2抑制作为RNV的潜在治疗策略.
主要方法:
- 在低氧条件下研究HRMEC和氧诱导视网膜病变 (OIR) 的小鼠模型.
- 使用了免疫光,染色体免疫沉降和双化酶记者分析.
- 采用EZH2抑制剂和siRNA用于基因沉默,并评估细胞增殖,迁移和血管生成.
主要成果:
- 缺氧增加了HRMEC和视网膜新血管中的EZH2和H3K27三甲基化.
- 抑制EZH2降低了HRMEC的扩散,迁移和血管生成.
- 以EZH2为媒介的H3K27三甲基化抑制了针对KDR的miR-221;EZH2抑制降低了KDR水平.
- 通过DZNeP抑制EZH2,在OIR小鼠中降低了RNV.
结论:
- EZH2-miR-221-KDR轴是RNV的一个关键调节器.
- 抑制EZH2表明了与RNV相关的疾病的治疗潜力.
更多相关视频
07:50Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina
Published on: August 29, 2018
9.4K
09:17Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
Published on: August 2, 2018
18.7K
相关概念视频
Regulation of Angiogenesis and Blood Supply
3.3K
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...
3.3K
Histone Modification
4.4K
4.4K
Histone Modification
15.9K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
15.9K
Chromatin Modification in iPS Cells
2.1K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
2.1K
Position-effect Variegation
7.0K
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
7.0K
Spreading of Chromatin Modifications
9.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
9.3K
