脏Angptl4是糖尿病进展性病中关键的纤维化分子
Swayam Prakash Srivastava1,2,3,4, Han Zhou1,2, Rachel Shenoi1
1Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
Science advances
|December 4, 2024
概括
血管蛋白类4 (ANGPTL4) 在糖尿病中驱动纤维化. 抑制ANGPTL4可以防止糖尿病病,减少炎症和损伤.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 糖尿病病 (DKD) 是糖尿病的一个主要并发症.
- 血管蛋白样4 (ANGPTL4) 在DKD病变发生过程中的作用尚不清楚.
- ANGPTL4参与脂蛋白代谢,具有多种生物效应.
研究的目的:
- 为了研究 podocyte 和管体特定的 ANGPTL4 在糖尿病纤维化中的作用.
- 阐明 ANGPTL4 导致 DKD 的分子机制.
- 评估抑制DKD中的ANGPTL4的治疗潜力.
主要方法:
- 利用ANGPTL4突变小鼠评估其在糖尿病引起的纤维化中的作用.
- 分析了分子通路,包括炎症,上皮层-介质细胞过渡 (EMT) 和线粒体功能.
- 在细胞中研究了ANGPTL4与Integrin β1的相互作用.
- 测试了一种向药理疗法,抑制脏ANGPTL4基因表达.
主要成果:
- 特定于足细胞和管状细胞的ANGPTL4是糖尿病脏中关键的纤维生成因子.
- ANGPTL4 缺乏保护小鼠免受糖尿病诱导的纤维化.
- 保护与减少炎症,EMT和线粒体损伤以及脂肪酸氧化增加有关.
- ANGPTL4 与 Integrin β1 相互作用,影响下游的信号通路.
- 针对脏ANGPTL4的制改善了糖尿病脏中的蛋白尿和纤维化.
结论:
- 在糖尿病脏病中,由足细胞和管状细胞衍生的ANGPTL4发挥着显著的纤维化作用.
- 抑制ANGPTL4代表了DKD的一个有前途的治疗策略.
- 了解ANGPTL4的分子相互作用,可以了解DKD的病原性.
更多相关视频
10:25Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
Published on: November 10, 2021
1.8K
08:15Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
496
相关概念视频
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
01:25Antihypertensive Drugs: Direct Renin Inhibitors
490
The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
490
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
477
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
477
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
385
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
385
01:23Dipeptidyl Peptidase 4 Inhibitors
171
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...
171
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
581
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
581