通过p-STAT1/NLRP3信号促进血管化
Lihe Lu1, Xiaoyu Liu2,3, Yuan Gong2,3
1Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
概括
向STING (干扰素基因刺激器) 可能治疗慢性病 (CKD) 中的血管化. STING的激活加剧了化,而它的抑制则减少了沉积,突出了STING/p-STAT1/NLRP3通路.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 腎臟病學 (nephrology) 是一種醫學.
背景情况:
- 血管化是慢性病 (CKD) 患者心血管死亡的主要危险因素.
- cGAS-STING通路与心血管疾病有关,DNA损伤会激活它,但其在CKD相关的血管化中的作用尚不清楚.
研究的目的:
- 在CKD条件下调查STING信号在血管化中的作用.
- 探索潜在的分子机制,包括STAT1和NLRP3.3的参与.
主要方法:
- 在血管化模型中检查了STING表达.
- 使用了STING敲除,药物抑制和敲除小鼠.
- 进行了RNA测序,西部抹杀和沉积试验.
- 研究了p-STAT1和NLRP3抑制的作用.
主要成果:
- 在血管化过程中,STING表达升高.
- 抑制或淘汰STING会减少细胞和组织中的沉积物,而激活会加剧化.
- 刺痛淘汰赛小鼠显示大动脉化减少.
- 确定了STING/p-STAT1/NLRP3信号轴作为一个关键的调解器,STING激活了p-STAT1和NLRP3.
结论:
- 在CKD中,STING在促进血管化方面发挥着至关重要的作用.
- 在这个过程中,STING/p-STAT1/NLRP3信号通路是重要的调解者.
- 向STING是一个潜在的治疗策略,用于CKD患者的血管化.
相关概念视频
01:16Calmodulin-dependent Signaling
5.0K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.0K
01:28Nitric Oxide Signaling Pathway
4.9K
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
4.9K
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
01:11IP3/DAG Signaling Pathway
11.7K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
11.7K
01:41Non-Canonical Wnt Signaling Pathways
7.2K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.2K
01:24Regulation of Angiogenesis and Blood Supply
2.5K
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...
2.5K