NOTCH2使状细胞对瘤亡因子α的炎症反应敏感

相关实验视频

Updated: Jul 12, 2025

08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

7.9K

Ernesto Canalis¹, Jungeun Yu², Vijender Singh³

¹Department of Orthopaedic Surgery, UConn Health, Farmington, Connecticut, USA; Department of Medicine, UConn Health, Farmington, Connecticut, USA; UConn Musculoskeletal Institute, UConn Health, Farmington, Connecticut, USA.

The Journal of biological chemistry

|October 21, 2023

概括

软骨细胞中NOTCH2的功能增强放大瘤亡因子α (TNFα) 信号,增加互白素-6 (IL6) 和炎症通路,有助于骨关节炎的发病.

科学领域:

分子生物学分子生物学
免疫学免疫学免疫学
类风湿病学类风湿病学

背景情况:

诺奇信号通路调节免疫和炎症反应.
痕信号与骨关节炎 (OA) 病变发生有关.
功能获取的NOTCH2突变对OA产生敏感性,但机制尚不清楚.

研究的目的:

调查NOTCH2功能增长在OA病变发生中的作用.
阐明NOTCH2与TNFα在体细胞中的相互作用的分子机制.

主要方法:

使用了带有NOTCH2功能的Notch2^tm1.1Ecan和Notch2^2.1Ecan鼠标模型.
在冠状细胞中分析了基因表达 (Il6,Il1b,Hes1,Hey1,Hey2,Heyl).
执行了电泳运动转移测试 (EMSA) 和RNA测序 (RNA-Seq).

主要成果:

NOTCH2功能增益增强了TNFα诱导的IL6和IL1B表达在软细胞中.
TNFα从DNA中取代了RBPJ,增加了IL6和减少了Notch目标基因 (Hes1,Hey1,Hey2,Heyl).
NOTCH2 增强了 TNFα 对 NF-κB 信号传递的影响,升调炎症和细胞路径.

结论:

NOTCH2的功能增强加剧了TNFα驱动的冠状细胞炎症.
这种相互作用通过增强的IL6和炎症通路激活促进了OA的发病.
准NOTCH2-TNFα交叉声可能为骨关节炎提供治疗策略.

关键词:

哈吉杜·切尼综合征 (Hajdu Cheney Syndrome) 是一种严重的疾病.介质素 6 介质素 6 介质素这种受体是Notch受体.冠状腺细胞冠状腺细胞细胞因子细胞因子这是一种炎症炎症炎症炎症.瘤亡因子 α α

相关概念视频

03:14

Notch Signaling Pathway

4.3K

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...

4.3K

01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

2.1K

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...

2.1K

02:26

NF-κB-dependent Signaling Pathway

7.5K

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...

7.5K

02:17

The Tumor Microenvironment

6.6K

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

6.6K

01:16

TGF - β Signaling Pathway

7.4K

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...

7.4K

01:24

Regulation of Angiogenesis and Blood Supply

2.6K

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...