加列-3通过TLR4/MyD88/NF-κB通路参与动脉性勃起功能障碍的炎症和纤维化
Guanbo Wang1, Ruiyu Li2, Chen Feng2
1Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Cell death discovery
|February 20, 2024
概括
加勒-3 (Gal-3) 抑制通过向TLR4/MyD88/NF-κB通路来减少动脉性勃起功能障碍 (A-ED) 中的炎症和纤维化. 这表明Gal-3是改善A-ED的潜在治疗标.
科学领域:
- 心血管科学 心血管科学
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 免疫学 免疫学 免疫学
背景情况:
- 加勒-3 (Gal-3) 与心血管纤维化和炎症有关.
- 动脉性勃起功能障碍 (A-ED) 涉及血管损伤和随后的功能障碍.
- 了解Gal-3在A-ED中的作用对于开发向疗法至关重要.
研究的目的:
- 在A-ED的老鼠模型中研究Gal-3对炎症和纤维化的影响.
- 阐明涉及TLR4/MyD88/NF-κB通路的潜在分子机制.
- 评估A-ED中Gal-3抑制的治疗潜力.
主要方法:
- 开发了一种使用动脉损伤和高脂肪饮食的新型A-ED大鼠模型.
- 分析了阴茎组织中的Gal-3,TLR4,MyD88和NF-κB-p65表达.
- 评估了洞内压力,eNOS表达和光滑肌肉含量.
- 使用Gal-3抑制剂修改的果果果真菌素 (MCP) 进行体内治疗.
- 在体外实验中进行了涉及Gal-3在洞体光滑肌细胞 (CCSMCs) 中的敲击.
主要成果:
- 在A-ED模型中,血管狭窄,Gal-3,TLR4,MyD88和NF-κB-p65表达增加.
- 这些变化与降低的洞内压力,eNOS表达和光滑肌肉含量相关,表明炎症和纤维化.
- 治疗MCP显著扭转了这些有害影响.
- 在体外,Gal-3 Knockdown降低了TLR4,MyD88和NF-κB-p65的表达,并减少了CCSMCs中的炎症.
结论:
- 加勒-3在促进A-ED的炎症和纤维化方面发挥着重要作用.
- TLR4/MyD88/NF-κB通路是调解Gal-3在A-ED中的作用的关键机制.
- 用MCP抑制Gal-3通过减轻血管损伤和功能障碍为A-ED提供了一个有希望的治疗策略.
相关概念视频
Intracellular Signaling Affects Focal Adhesions
2.7K
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...
2.7K
Nitric Oxide Signaling Pathway
5.0K
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...
5.0K
The JAK-STAT Signaling Pathway
8.9K
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...
8.9K
TGF - β Signaling Pathway
7.4K
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...
7.4K
NF-κB-dependent Signaling Pathway
7.4K
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...
7.4K
Regulation of Angiogenesis and Blood Supply
2.6K
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...
2.6K


