β-1,4 GalT-V インタラクトーム-潜在的治療標的と癌および心血管および炎症疾患を誘発する経路のネットワーク
Subroto Chatterjee1, Dhruv Kapila1, Priya Dubey1
1The Helen B Taussig Heart Center, Cardiovascular Innovation Laboratory, Division of Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
International journal of molecular sciences
|August 28, 2025
まとめ
UDP-Gal-β-1, 4 ギャラクソシルトランスフェラーゼ-V (GalT-V) は,がんと炎症に関わる細胞経路を調節する. Sp-1/GalT-V軸をターゲットにすることで 結腸直腸がんや動脈硬化などの 治療戦略が生まれます
科学分野:
- 生化学と分子生物学
- 細胞生物学
- 癌 生物学
背景:
- UDP-Gal-β-1, 4 ギャラクソシルトランスフェラーゼ-V (GalT-V) は,脂質媒介体であるラクソシルセラミド (LacCer) を合成する.
- LacCerは酸化ストレスと炎症経路を活性化し,細胞増殖,移動,血管新生,自己死,アポトーシスに影響を与えます.
- GalT- V遺伝子発現は,重要なO- GlcNAcylated核因子である転写因子Sp-1によって調節される.
研究 の 目的:
- Sp-1/GalT-V軸が病気のフェノタイプに与える役割について詳しく説明する.
- Sp-1,Notch-1,Wnt-1を標的とした治療戦略について議論します.
- 治療対象としてβ-1,4-GalT-Vインタラクトムの可能性を調査する.
主な方法:
- GalT-V,Sp-1,および関連するシグナル伝達経路に関する既存の文献のレビュー
- VEGF独立経路を含む血管新生におけるGalT-Vの役割の分析
- GalT-Vインタラクトームと関連するシグナル分子を標的とした治療方法の検討.
主要な成果:
- Sp-1/GalT-V軸は血管新生において重要な役割を果たし,潜在的にノッチ-1のグリコシル化により,膠腫のような幹細胞の分化を促進する.
- LacCerはVEGF独立の血管新生を誘導し,腫瘍組織で高濃度が見られる.
- β-1,4-GalT-Vインタラクトームの調節不良は,様々な疾患における制御されない増殖,血管新生,および炎症に寄与する.
結論:
- 増加したβ-1,4- GalT- V発現は,大腸がんと動脈硬化症の潜在的な診断バイオマーカーです.
- Sp-1/GalT-V軸と関連する経路をターゲットにすることで,癌,心血管,炎症性疾患の新たな治療戦略が提供されます.
- 喫煙や食事などの環境要因はβ-1,4-GalT-V発現に影響し,病気管理におけるライフスタイルの重要性を強調しています.
さらに関連する動画
13:18Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma
Published on: March 3, 2023
1.3K
06:56A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4
Published on: March 10, 2018
13.9K
関連する概念動画
01:17Intracellular Signaling Affects Focal Adhesions
2.8K
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...
2.8K
01:15Activation of Integrins
3.6K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.6K
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.8K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.8K
01:10Integrins
4.1K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
4.1K
01:19Interactions Between Signaling Pathways
6.4K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.4K
01:23Dipeptidyl Peptidase 4 Inhibitors
252
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
252