ALKBH5通过调解FOXM1 M6A脱甲基化来调节角膜新血管化
Wei Wang1, Hua Li1, Yiyong Qian1
1Department of Ophthalmology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Investigative ophthalmology & visual science
|October 23, 2024
概括
ALKBH5脱甲基化通过向FOXM1.1来调节角膜新血管化 (CNV). 抑制ALKBH5可降低神经神经病毒和炎症,为眼部疾病提供潜在的治疗策略.
科学领域:
- 眼科医生 眼科 眼科
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 角膜新血管化 (CNV) 是视力障碍的一个重要原因.
- N6-甲基氨酸 (m6A) 修饰在各种生物过程中发挥作用,包括血管生成.
- 在CNV中ALKBH5-介导的m6A脱甲基化的特定作用仍未得到充分研究.
研究的目的:
- 研究ALKBH5在CNV中的调节功能.
- 阐明ALKBH5在CNV病变发生过程中的潜在分子机制.
- 评估针对ALKBH5进行中枢神经炎治疗的治疗潜力.
主要方法:
- 使用角膜性烧伤建立了CNV的小鼠模型.
- 量化m6A水平和m6A相关酶的mRNA表达.
- 利用小干扰RNA在体内和体外敲击ALKBH5.
- 在人静脉内皮细胞 (HUVECs) 中评估细胞增殖,迁移和管形成.
- 使用双化酶和甲基化RNA免疫沉-qPCR试验检查了ALKBH5和FOXM1之间的相互作用.
主要成果:
- ALKBH5的表达增加,而总m6A水平在CNV角膜和IL-6诱导的HUVEC中降低.
- ALKBH5的敲击缓解了 CNV,减少了炎症,并抑制了 HUVEC 的增殖,迁移和管道形成.
- ALKBH5 枯竭增加了FOXM1 mRNA上的m6A水平,导致FOXM1表达的减少.
- 过度表达FOXM1逆转了ALKBH5耗尽的影响.
结论:
- 通过ALKBH5介导的FOXM1的m6A脱甲基化是中枢神经病毒进展的关键调节者.
- ALKBH5 作为 CNV 中的一种亲血管性因子.
- 准ALKBH5是一个有前途的治疗策略,用于管理角膜新血管化.
相关概念视频
01:24Regulation of Angiogenesis and Blood Supply
2.5K
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...
2.5K
02:33Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
01:15Receptor Downregulation in MVBs
2.0K
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...
2.0K