相关实验视频

Updated: Jul 15, 2025

Isolation of Murine Retinal Endothelial Cells for Next-Generation Sequencing

Isolation of Murine Retinal Endothelial Cells for Next-Generation Sequencing

Published on: October 11, 2021

内皮细胞SMAD6平衡Alk1功能,调节附着结和肝血管发育

Molly R Kulikauskas¹, Morgan Oatley², Tianji Yu²

¹Cell Biology and Physiology Curriculum, The University of North Carolina, Chapel Hill, NC 27599, USA.

Development (Cambridge, England)

|October 3, 2023

概括

抑制性SMAD6通过调节内皮细胞中ALK1信号传递来预防血管缺陷. 失去SMAD6会导致出血,但平衡的ALK1活性是血管发育的关键.

科学领域:

血管生物学血管生物学
细胞信号传递细胞信号传递
发展生物学发展生物学

背景情况:

骨形态遗传蛋白 (BMP) 信号传递对于血管的形成和功能至关重要.
通过BMP途径组件调节血管发育的确切机制尚不清楚.

研究的目的:

研究胚胎血管发育期间内皮细胞中抑制性SMAD6的作用.
阐明SMAD6如何调节内皮细胞中激素受体类激酶1 (ALK1) 介导的信号传递.

主要方法:

使用小鼠模型进行体内研究,在内皮细胞中对Smad6和Alk1进行基因操纵.
细胞测试检查内皮细胞结合点,屏障功能和信号通路 (PI3K,阿克托米奥辛收缩性).

主要成果:

在内皮细胞中,SMAD6作为ALK1信号的负调节剂,防止胚胎肝血管中的失态生殖和出血.
SMAD6的丧失导致内皮细胞结位不稳定和屏障功能受损,可以通过降低Alk1基因剂量来挽救.
从机制上讲,SMAD6的损失通过改变PI3K信号传递和actomyosin收缩性来破坏内皮细胞结合点.

结论:

在内皮细胞中,SMAD6对于维持适当的ALK1信号幅度至关重要,这对血管完整性至关重要.
ALK1作为"金头发"通道,需要平衡的信号传递来维持正常的血管发育,SMAD6作为关键调节器.
这种SMAD6-ALK1轴的失调有助于血管缺陷,突出其在发育和潜在的病变性血管生成中的重要性.

关键词:

在ALK1/ACVRL1中使用.粘附于连接点的结合点.在BMP中,BMP是BMP.契约性契约性是指契约性.内皮细胞是内皮细胞.肝脏的发育肝脏的发育肝脏的侧鼻状.在PI3K中,PI3K是指PI3K.在SMAD6中,我们可以看到SMAD6.血管屏障血管屏障血管屏障

更多相关视频

Directed Differentiation of Hemogenic Endothelial Cells from Human Pluripotent Stem Cells

Directed Differentiation of Hemogenic Endothelial Cells from Human Pluripotent Stem Cells

Published on: March 31, 2021

Quantitation of Endothelial Cell Adhesiveness In Vitro

Quantitation of Endothelial Cell Adhesiveness In Vitro

Published on: June 18, 2015

相关概念视频

Regulation of Angiogenesis and Blood Supply

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...

Notch Signaling Pathway

Notch Signaling Pathway

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...

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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...

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.

Intracellular Signaling Affects Focal Adhesions

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...

Anchoring Junctions

Anchoring Junctions

Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...