在男性肺动脉高血压患者中对长非编码RNAX无活性特异转录表达的失调
Brandon L Carman1, Shanshan Qin1, Dan N Predescu1
1Division of Pulmonary, Critical Care and Sleep Medicine, Rush University Medical Center, Chicago, Illinois.
The American journal of pathology
|May 5, 2024
概括
男性肺动脉高血压 (PAH) 细胞中Xist长非编码RNA的增加通过降低Klf2.的调节驱动增殖. 这一发现揭示了PAH的性别偏见,并为这种心血管疾病提供了新的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 肺动脉高血压 (PAH) 是一种性别偏差的疾病,女性的风险更高.
- 长非编码RNA X-无活性特异性转录 (Xist) 涉及两性变异,可能在PAH的发病过程中发挥作用.
研究的目的:
- 研究男性肺动脉内皮细胞 (EC) 中Xist表达的作用,来自PAH患者 (ECPAH).
- 阐明Xist影响ECPAH扩散并导致PAH性别偏差的分子机制.
主要方法:
- 在男性ECPAH中分析Xist表达水平.
- 分子,生化,形态和功能测试以研究Xist对ECPAH的影响.
- 研究Xist与EH,EZH2和Klf2.2的相互作用.
- 对EHITSN触发的信号通路 (p38/Elk1/c-Fos) 和细胞循环调节者的分析.
主要成果:
- 与低Xist水平相比,男性ECPAH表现出明显更高的Xist表达.
- 增加的Xist表达与男性ECPAH的增强的生殖潜力有关.
- 囊上调节通过EHITSN-EZH2相互作用减少了Krueppel样因子2 (Klf2) 表达.
- EHITSN触发信号和Xist-EZH2-Klf2交叉声被确定为男性ECPAH扩散的关键驱动因素.
结论:
- 在男性ECPAH中,囊的上调有助于促进扩散,从而促进疾病病理.
- Xist-EZH2-Klf2轴和相关的信号通路代表了PAH性别变态的基础新机制.
- 向Xist或其下游影响者可能为PAH提供治疗策略.
相关概念视频
lncRNA - Long Non-coding RNAs
8.6K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.6K
Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K
Alternative RNA Splicing
21.1K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.1K
RNA Splicing
56.3K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.3K
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
148
Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
148
Pulmonary Hypertension: Classification and Pathogenesis
173
Pulmonary hypertension (PH) is a severe health condition in which the mean pulmonary arterial pressure increases to 25 mmHg or more, even when the body is at rest. This high pressure in the blood vessels that transport blood from the heart to the lungs can cause various symptoms, including shortness of breath, can lead to right heart failure, and significantly affect the overall quality of life.
There are various classifications for PH, each relating to different underlying causes and also...
There are various classifications for PH, each relating to different underlying causes and also...
173


