IL-1β/STAT1轴通过对转录激活剂GLIS2的隔离抑制STAT3功能,从而导致术后血管功能障碍
Yi Wang1, Liang Cao1, Ke Wang2
1Department of Anesthesiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
International immunopharmacology
|October 17, 2024
概括
手术后的炎症会引发内皮功能障碍和血栓形成. 互白素-1β激活了STAT1,从而阻断了STAT3的作用.
科学领域:
- 血管生物学和血栓形成
- 分子信号通路 分子信号通路
- 炎症反应机制 炎症反应机制
背景情况:
- 手术诱导的内皮功能障碍对血栓形成有显著的贡献.
- 信号转换器和转录激活器 (STAT) 家族信号在术后血管反应中的作用尚不清楚.
- 确定关键的分子通路对于制定预防术后血栓形成的策略至关重要.
研究的目的:
- 阐明手术创伤后血管功能障碍背后的信号机制.
- 识别潜在的分子标,用于预测或预防术后血栓形成.
- 研究STAT信号在调解手术创伤的炎症反应中的作用.
主要方法:
- 内皮细胞与手术后创伤模型中的血清共同培养.
- 生物信息学分析被用来识别相关的信号通路.
- 在小鼠模型中评估了炎症媒介水平,STAT激活和蛋白质相互作用.
主要成果:
- 生物信息学分析揭示了手术创伤与涉及血栓,白内素,细胞因子和STAT信号传递的途径之间的联系.
- 在手术后创伤血清中检测到高的炎症媒介.
- 干白素-6 (IL-6) 激活了STAT3,促进了内皮增殖,而干白素-1β (IL-1β) 激活了STAT1,抑制了STAT3.
- 鉴定出gli-similar 2 (GLIS2) 是一个STAT3协活性剂,但STAT1抑制了GLIS2-STAT3的相互作用,抑制了内皮增殖.
结论:
- 干白素-1β (IL-1β) 诱导的STAT1激活破坏了GLIS2-STAT3相互作用,降低了STAT3的转录活性.
- 这种干扰导致内皮功能障碍,并导致手术创伤后的血栓形成.
- 准IL-1β/STAT1/GLIS2/STAT3轴为预防术后内皮功能障碍和血栓形成提供了一个新的治疗策略.
相关概念视频
01:20The 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
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
01:16TGF - 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
01:17Intracellular 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
01:22Amplifying Signals via Enzymatic Cascade
8.3K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.3K
01:22PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K