痕信号增强了CTEPH中PASMC的扩散和血管重塑
Salamaiti Aimaier1, Ailiman Mahemuti1, Refukaiti Abuduhalike1
1Department of Heart Failure, First Affiliated Hospital of Xinjiang Medical University, 830054, Urumqi, China.
Open life sciences
|March 2, 2026
概括
切口信号激活通过增加光滑肌肉细胞增殖,促进慢性血栓栓塞性肺高血压 (CTEPH) 中的肺血管重塑. 通过DAPT抑制这种途径减少了重塑,这表明了CTEPH的潜在治疗策略.
科学领域:
- 心血管研究研究心血管研究
- 分子生物学分子生物学
- 肺高血压是什么意思 肺高血压
背景情况:
- 肺血管改造 (PVR) 是慢性血栓栓塞性肺高血压 (CTEPH) 的一个关键特征.
- 诺奇信号通路因其在血管疾病中的作用而越来越受认可.
研究的目的:
- 在CTEPH的老鼠模型中调查Notch信号在PVR中的作用.
- 评估抑制CTEPH中的Notch信号的治疗潜力.
主要方法:
- 使用了CTEPH的老鼠模型.
- 测量了血液动力学参数 (RVSP,MPAP) 并进行了组织学分析.
- 通过Western blot评估了蛋白质表达 (Notch1,Notch3,Jagged1,Hes1,PCNA,α-SMA) 的情况.
- 服用DAPT,一种g-分泌酶抑制剂,以评估Notch通路的抑制.
主要成果:
- 在CTEPH大鼠中,Notch通路蛋白质 (Notch1,Notch3,Jagged1,Hes1) 和中间壁厚度 (MWT%) 的增加.
- VPA治疗进一步增加了诺奇蛋白和PVR标记物.
- DAPT治疗显著降低了Notch通路蛋白,MWT%,以及光滑肌肉细胞增殖标志物 (PCNA,α-SMA).
结论:
- 诺奇信号的激活促进了肺动脉平滑肌肉细胞的增殖,有助于CTEPH中的PVR.
- 在CTEPH大鼠模型中,通过DAPT抑制Notch信号有效地缓解了血管重塑.
- 准Notch路径为CTEPH治疗提供了一个有前途的治疗途径.
相关概念视频
Notch Signaling Pathway
6.7K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.7K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.5K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.5K
Regulation of Angiogenesis and Blood Supply
3.8K
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...
3.8K
mTOR Signaling and Cancer Progression
4.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.9K
PI3K/mTOR/AKT Signaling Pathway
5.9K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.9K
Interactions Between Signaling Pathways
7.5K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.5K


