与脂肪细胞相关的葡萄糖皮质体信号调节正常的纤维细胞功能,这种功能在炎症性关节炎中会丧失
Heather J Faust1, Tan-Yun Cheng1, Ilya Korsunsky1,2,3
1Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nature communications
|November 14, 2024
概括
健康的纤维细胞功能依赖于皮质醇信号和脂肪细胞. 疾病中这种信号的丧失有助于组织损伤,突出了纤维状况的新治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 代谢性疾病 代谢性疾病
背景情况:
- 纤维细胞对组织健康至关重要,但可以引起疾病.
- 人们对恒常性纤维细胞功能调节的理解仍然不充分.
研究的目的:
- 为了确定健康的突纤维细胞功能的关键调节者.
- 研究皮质醇和脂肪细胞在维持纤维细胞平衡中的作用.
主要方法:
- 合成纤维细胞的RNA测序.
- 在体内基因操纵 (纤维细胞特异性葡萄皮质受体缺失).
- 使用细胞因子 (TNF,TGF-β1) 的体外研究.
主要成果:
- 健康的纤维细胞表现出增强的脂肪酸代谢和脂质运输.
- 皮质醇被确定为健康纤维细胞表型的关键调节剂.
- 脂肪细胞的枯竭和葡萄糖皮质体受体的缺失会使小鼠的关节炎恶化.
- 皮质醇信号减轻了细胞因子诱导的矩阵重塑,这反过来抑制了皮质醇信号.
结论:
- 脂肪细胞和皮质醇信号传递对于保持健康的突纤维细胞状态至关重要.
- 这种途径的失调有助于疾病的发病.
- 准皮质醇信号可能为纤维性疾病提供治疗效益.
相关概念视频
The JAK-STAT Signaling Pathway
8.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.7K
TGF - β Signaling Pathway
7.2K
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...
7.2K
Inflammatory Response
1.9K
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
1.9K
Intracellular Signaling Affects Focal Adhesions
2.6K
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...
Some...
2.6K
Inflammation
52.8K
Overview
52.8K
T Cell Types and Functions
954
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
954


