SR9009通过NR1D1/NLRP3/IL-1β通路减轻与炎症相关的NPMSC热和IVDD
Ze-Nan Huang1, Jing Wang2, Ze-Yu Wang3
1Department of Orthopedics, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 200072, Shandong Province, China.
iScience
|May 1, 2024
概括
核受体NR1D1的表达随着椎间盘退化而下降. 激活NR1D1通过调节NLRP3 / IL-1β通路来抑制炎症并保护磁盘退化.
科学领域:
- 生物医学科学 生物医学科学
- 组织工程是组织工程.
- 炎症研究 炎症研究
背景情况:
- 椎间盘退化涉及复杂的炎症过程.
- 核受体NR1D1在磁盘生物学和退化中的作用尚不清楚.
- NR1D1参与调节生物节律和炎症反应.
研究的目的:
- 研究NR1D1在椎间盘退化中的作用.
- 探索NR1D1激活在缓解磁盘退化中的治疗潜力.
- 阐明NR1D1对炎症和细胞外矩阵 (ECM) 恒温的作用的分子机制.
主要方法:
- 在核脉组织中量化NR1D1表达.
- 使用SR9009进行NR1D1的体外激活,并评估NLRP3炎症酶组合和IL-1β产生.
- 对ECM合成标记物的评估.
- 在体内研究以评估NR1D1激活对磁盘退化的影响.
- 涉及IL-1β和NLRP3的促进体结合试验的机制研究.
主要成果:
- NR1D1在核脉中表现出节奏表达,并在磁盘退化过程中减少.
- NR1D1激活抑制了NLRP3炎症酶组合和IL-1β产生,同时增加了ECM合成在体外.
- 在体内激活NR1D1表明对磁盘退化有保护作用.
- 发现NR1D1与IL-1β和NLRP3促进体结合,涉及NR1D1/NLRP3/IL-1β通路.
- NR1D1的激活减少了IL-1β的分泌,并缓解了LPS诱导的NPMSC热,从而保持了ECM的完整性.
结论:
- NR1D1在维持椎间盘健康方面发挥着至关重要的作用.
- 激活NR1D1为椎间盘退化提供了一个有希望的治疗策略.
- NR1D1/NLRP3/IL-1β通路是脊椎间盘炎症和退行的一个关键调解器.
更多相关视频
相关概念视频
02:26NF-κB-dependent Signaling Pathway
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 heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:28Inflammatory Response
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,...
01:24T Cell Types and Functions
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...