在患有类风湿性关节炎的患者中,对细胞压力的内质网膜依赖的亡反应
Aleksandra Kucharska-Lusina1, Maciej Skrzypek1, Agnieszka Tokarczyk1
1Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland.
International journal of molecular sciences
|March 27, 2025
概括
类风湿性关节炎患者对亡的敏感性增加,这与细胞内网膜 (ER) 应激和未折叠蛋白质响应 (UPR) 路径激活有关. 这一发现表明了RA的潜在新诊断标志物和治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 风湿性关节炎 (RA) 是一种慢性自身免疫性疾病,导致炎症性多关节炎和潜在的残疾.
- 目前的RA治疗可以控制症状,但不能完全恢复.
- 细胞内膜网膜 (ER) 应激和未折叠蛋白响应 (UPR) 激活与RA病变发生有关.
研究的目的:
- 评估类风湿性关节炎 (RA) 患者的亡水平.
- 调查UPR激活和诱导亡之间的相关性,作为RA的潜在诊断或治疗标.
主要方法:
- 对31名RA患者和30名健康对照的外周血液单核细胞 (PBMC) 的分析.
- 用RT-qPCR测量ER压力标志物的mRNA水平 (eIF2α,BBC3/PUMA,TP53).
- 彗星测定以评估DNA损伤和流细胞测量以评估亡诱导.
主要成果:
- 在RA患者中观察到eIF2α,BBC3 (PUMA) 和TP53的mRNA水平升高.
- 关节炎患者的DNA尾部百分比增加了37.78% (彗星测定) 和高达40.17%的caspase-3水平.
- 来自RA患者的PBMC细胞显示,与对照人群相比,在早期亡中细胞的百分比提高了40.23%.
结论:
- 关节炎患者对诱导亡的敏感性显著增加.
- UPR通路的激活与RA中亡的增加有关.
- 这些发现支持ER压力和UPR标志物的潜力,用于早期RA诊断和向治疗的开发.
更多相关视频
相关概念视频
01:31Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
01:24T Cell Types and Functions
724
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...
724
01:37The Unfolded Protein Response
4.3K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.3K
01:20The JAK-STAT Signaling Pathway
8.6K
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...
8.6K
01:17The Extrinsic Apoptotic Pathway
5.7K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
5.7K
01:28Inflammatory Response
1.7K
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,...
1.7K