降低EZH2的调节促进上皮细胞衰老和脏衰老
Yingying Zhang1,2, Chen Yu2, Ewud Agborbesong1,3
1Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
概括
这项研究揭示了增强性同源2 (EZH2) 通过调节p16和p21.2的作用来防止脏衰老和细胞衰老. 降低EZH2水平加速这些衰老过程,形成负反循环.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 上皮细胞衰老和衰老是关键的研究领域.
- 表观遗传调节在这些过程中的作用尚未完全理解.
- 增强体质同类物2 (EZH2) 的增强剂,一种基因素甲基转移酶,涉及病理生理学.
研究的目的:
- 研究EZH2在衰老和细胞衰老中的作用.
- 阐明EZH2影响这些过程的表观遗传机制.
- 确定EZH2抑制对衰老标志物的影响.
主要方法:
- 在老年和辐射诱导的小鼠脏和人类皮管状上皮细胞 (RCTE) 中评估了EZH2表达.
- 使用EZH2抑制剂 (3-DZNeP) 研究其对衰老标记物的影响 (p16,p21).
- 研究了EZH2通过H3K27me3的转录抑制机制及其与p53和ATM的相互作用.
主要成果:
- 在老年和辐射诱导的脏和RCTE细胞中,EZH2表达通过蛋白质体降解而降低.
- 抑制EZH2促进管状细胞衰老和脏衰老,增加p16和p21的表达.
- EZH2通过H3K27me3抑制p16转录,通过p53/ATM相互作用抑制p21转录.
- 抑制ATM以p53依赖的方式降低EZH2酸化和促进剂结合.
结论:
- EZH2对于预防脏衰老和DNA损伤引起的衰老至关重要.
- 在衰老和衰老过程中减少EZH2不稳定会产生负反循环.
- 这些发现突出了EZH2作为与年龄相关的脏疾病的潜在治疗点.
更多相关视频
13:59A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
Published on: August 12, 2018
8.0K
06:48Quantitative Real-Time Polymerase Chain Reaction Evaluation of MicroRNA Expression in Kidney and Serum of Mice with Age-Dependent Renal Impairment
Published on: April 29, 2022
2.2K
相关概念视频
01:37Epigenetic Regulation
2.9K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
2.9K
02:23Abnormal Proliferation
4.3K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.3K
01:23Negative Regulator Molecules
35.0K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.0K
01:10Nephrons
1.5K
The kidneys are intricate organs with millions of working units known as nephrons. Each nephron features two major structures: the renal corpuscle, which facilitates blood plasma filtration, and the renal tubule, which handles the glomerular filtrate. Blood supply is directly linked to the nephrons. The renal corpuscle consists of the glomerulus, a capillary network, and the Bowman's capsule, a double-walled epithelial structure that encases the glomerulus. The filtering of blood plasma...
1.5K
01:20The Retinoblastoma Gene
4.0K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.0K