TRIM11通过促进HOXB9无处置和诱导NF-κB信号通路来调节败血症的进展
Jiaqi Gan1, Wei Zhang2, Fei Pan1
1Department of General Medicine, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai, 201199, China.
Molecular biology reports
|February 4, 2025
概括
这项研究表明,TRIM11和HOXB9在败血症的发病过程中起着至关重要的作用. 通过通过ubiquitination抑制HOXB9诱导的炎症和亡,TRIM11可以缓解败血症.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 败血症的发病原因
背景情况:
- 败血症是一种危及生命的器官功能障碍,其原因是宿主对感染的反应失调.
- 炎症和亡是败血症中关键的病理过程.
- 在败血症中TRIM11和HOXB9的作用仍然不完全理解.
研究的目的:
- 为了研究TRIM11和HOXB9在败血症发病的功能.
- 为了阐明它们对炎症,亡和NF-κB信号通路的影响.
- 评估TRIM11作为潜在的败血症生物标志物.
主要方法:
- 使用公共数据库对与败血症相关的TRIM家族基因进行查.
- 对TRIM11作为败血症生物标志物的ROC分析.
- 在体外实验中,使用用脂聚糖 (LPS) 刺激的THP-1细胞进行实验.
- 流细胞测量,ELISA和西部斑点来评估细胞亡和炎症性细胞因子.
- 调查TRIM11-HOXB9全域化相互作用和NF-κB通路调节.
主要成果:
- 在有高诊断价值的败血症患者中增加TRIM11表达.
- TRIM11 knockdown缓解了LPS诱导的亡和炎症;HOXB9 knockdown加剧了这些影响.
- 同时下调TRIM11和HOXB9平衡的败血症相关反应.
- TRIM11通过ubiquitination逆转了HOXB9诱导的NF-κB激活,揭示了一个新的调节机制.
结论:
- TRIM11和HOXB9相互作用,以调节败血症中的炎症和亡.
- TRIM11作为HOXB9的负调节剂,调节NF-κB通路.
- 这些发现为治疗败血症的潜在治疗策略提供了新的见解.
相关概念视频
NF-κB-dependent Signaling Pathway
7.2K
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...
NF-κB-dependent Signaling Mechanism
The...
7.2K
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
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.0K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.0K
PI3K/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
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
The 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


