荷莫平素通过调节YES相关蛋白1调节高葡萄糖诱导的血管内皮屏障功能障碍,从而缓解高葡萄糖诱导的血管内皮屏障功能障碍
Xulu Li1, Jingwen Wang1, Lei Wang1
1School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 639 Longmian Avenue, Nanjing 211198, China.
概括
同类植物素 (HPG) 通过调节YAP1/SIRT1/HMGB1通路来保护血管内皮壁 (VE) 免受高葡萄糖损伤. 这种天然化合物在治疗糖尿病大血管并发症方面表现有前途.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 血管内皮 (VE) 屏障功能障碍是糖尿病大血管并发症的关键因素.
- 来自Salvia plebeia R.Br.的同植物素 (HPG) 已表现出内皮保护性,但其在糖尿病疾病中的机制尚不清楚.
研究的目的:
- 研究HPG对高葡萄糖 (HG) 治疗的人类静脉内皮细胞 (HUVEC) 和1型糖尿病 (T1D) 的小鼠在VE屏障功能上的保护作用.
- 阐明HPG作用的潜在分子机制.
主要方法:
- 在体外测试 (西部涂抹,RT-qPCR,免疫光,跨内皮电阻,穿孔透性) 评估了HPG对HUVECs的影响.
- 在体内研究中,使用HPG或EX-527 (SIRT1抑制剂) 给T1D小鼠进行测试,以评估治疗疗效.
主要成果:
- HPG上调VE-cadherin,ZO-1,ocludin和claudin-1,降低了HG-HUVEC中的透性和HMGB1转位.
- HPG抑制了YAP1酸化,促进了核转位,并增强了YAP1-SIRT1相互作用,直接相互作用得到证实.
- 在T1D小鼠中,HPG改善了葡萄糖/脂质代谢,减少了氧化应激/炎症,增强了内皮屏障功能,并减轻了大动脉损伤,EX-527可以逆转这些影响.
结论:
- 通过YAP1/SIRT1/HMGB1通路,HPG保护高葡萄糖诱导的VE屏障功能障碍.
- 在糖尿病大血管并发症的管理中,HPG是潜在的治疗候选者.
相关概念视频
Glucose Homeostasis: Regulation of Blood Glucose
4.5K
Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
4.5K
Hormones Regulating Blood Glucose
7.1K
Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
In addition to accelerating glucose uptake and utilization, insulin has...
7.1K
Regulated Protein Degradation
8.9K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K
Regulated Protein Degradation
3.2K
3.2K
Covalently Linked Protein Regulators
9.7K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.7K
Covalently Linked Protein Regulators
2.0K
2.0K


