对PDGFR-β受体亚单元表达的反感性寡核酸抑制,直接抑制了内密结的发生
M G Sirois1, M Simons, E R Edelman
1Harvard-MIT Division of Health Sciences and Technology, Cambridge, Brigham and Women's Hospital (E.R.E.), Boston, Mass, USA. mgsirois@mit.edu
Circulation
|February 4, 1997
概括
针对血小板衍生的生长因子-β受体 (PDGFR-β) 的反感性寡核酸可显著降低血管损伤后的新因子形成. 抑制PDGFR-β表达或PDGF-BB的激活是血管疾病的潜在治疗策略.
科学领域:
- 血管细胞生物学 血管细胞生物学
- 血管疾病的分子机制
- 基因治疗的应用 基因治疗的应用
背景情况:
- 血管细胞生物学的进步为血管疾病的病理生理学提供了信息.
- 反感性寡核酸基因疗法识别了细胞增殖的关键蛋白质.
- 血管疾病中的化学作用因子和受体仍未得到充分研究.
研究的目的:
- 评估反感性寡核酸降低PDGFR-β表达的能力.
- 确定PDGFR-β对新极端形成的贡献.
- 研究血管增殖的治疗策略.
主要方法:
- 针对PDGFR-β mRNA的反感性寡核酸的周周血管注射.
- 在受伤的动脉中量化PDGFR-β蛋白表达.
- 评估neointimal形成及其与PDGFR-β表达的相关性.
主要成果:
- 反感性寡核酸几乎取消了PDGFR-β蛋白表达.
- 在两种不同的反意义序列下,Neointimal形成减少了80%和60%.
- 新极值形成与PDGFR-β表达呈指数相关.
结论:
- 肌肉最大增殖取决于PDGFR-β的过度表达和PDGF-BB的激活.
- 抑制PDGFR-β或PDGF-BB可以抑制neointimal的形成.
- 向PDGFR-β代表了血管增殖性疾病的潜在治疗途径.
相关概念视频
RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
Regulation of Angiogenesis and Blood Supply
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 hydroxylase and factor...
GPCR Desensitization
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...


