间歇性细胞外低pH环境对人类静脉内皮细胞活动的影响
Ryota Nishida1, Tomoaki Fukui1, Kenichi Sawauchi1
1Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
PloS one
|September 16, 2025
概括
间歇性低pH暴露,模仿穿皮CO2疗法,增强内皮细胞功能,促进血管生成. 这一过程由ERK1/2 MAPK和PI3K/AKT信号通路介导,这对于组织修复至关重要.
科学领域:
- 生物医学工程 生物医学工程
- 细胞生物学 细胞生物学
- 生理学 生理学 生理学
背景情况:
- 透皮CO2治疗通过增强血管生成加速骨折愈合和骨形成.
- 在二氧化碳治疗的益血管性作用的基础上,精确的分子机制在很大程度上仍未被阐明.
- 治疗包括局部组织pH的暂时,间歇性下降.
研究的目的:
- 研究人类静脉内皮细胞 (HUVEC) 对间歇性低pH刺激的细胞和分子反应.
- 为了确定间歇性酸性条件是否会激活内皮细胞,类似于酸性预条件.
- 阐明通过间歇性低pH的内皮细胞激活所涉及的信号通路.
主要方法:
- 在三个条件下培养HUVEC:间歇性低pH (每天pH7.0 20分钟),连续低pH和控制pH (7.4).
- 评估细胞的增殖,管形成和迁移.
- 通过西方涂抹和基因表达分析分析了关键血管生成因子 (VEGF,VEGFR2,CD31) 和信号分子 (ERK1/2,AKT) 的蛋白质和基因表达.
- 使用特定抑制剂 (ERK1/2的U0126,AKT的LY294002) 来探测途径的参与.
主要成果:
- 与对照组相比,间歇性低pH暴露显著增强了HUVEC管的形成和迁移.
- 持续的低pH也增加了管形成,而这两种低pH条件都提高了CD31基因表达.
- 在间歇性组中观察到血管内皮生长因子 (VEGF) 和VEGF受体2的升级表达.
- 在低pH条件下,细胞外信号调节激酶1和2 (ERK1/2) 和蛋白激酶B (AKT) 途径的激活显著增加.
结论:
- 间歇性低pH刺激有效地增强内皮细胞的增殖,迁移和管形成.
- ERK1/2 MAPK和PI3K/AKT信号通路是响应间歇性酸性条件时内皮细胞激活的关键介质.
- 研究结果提供了关于皮肤间CO2治疗如何促进血管新生和组织修复的机制性见解.
更多相关视频
09:39Development and Characterization of In Vitro Microvessel Network and Quantitative Measurements of Endothelial [Ca2+]i and Nitric Oxide Production
Published on: May 19, 2016
9.0K
07:56Monitoring Changes in Human Umbilical Vein Endothelial Cells upon Viral Infection Using Impedance-Based Real-Time Cell Analysis
Published on: May 5, 2023
745
相关概念视频
Stomach pH Regulation
The human body carefully regulates the internal pH of different organs to maintain homeostasis. For example, while the blood plasma maintains a neutral pH of 7, the stomach lumen has an acidic pH of 1.5 - 3.5. The low pH of stomach lumen helps kill pathogens in the food and break down complex food molecules.
The acid-secreting gastric mucosal epithelial cells (parietal cells) lining the stomach lumen maintain the low pH in the lumen. Numerous ion transporters and channels on these parietal...
The acid-secreting gastric mucosal epithelial cells (parietal cells) lining the stomach lumen maintain the low pH in the lumen. Numerous ion transporters and channels on these parietal...
pH Regulation in Cells
pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
pH Homeostasis
Acid-base homeostasis is essential for maintaining normal physiological activities in humans. The pH of various body fluids is strictly regulated because it is critical for the optimal activity of enzymes involved in metabolic reactions. Enzymes are basically proteins, so, any significant change in pH can affect their structure and activity. In humans, pH is regulated using three primary mechanisms— chemical buffer systems, respiratory regulation, and renal regulation.
Respiratory Regulation of...
Respiratory Regulation of...
Autoregulation of Blood Flow
Autoregulation mechanisms are characterized by their inherent capacity for self-regulation without necessitating specific nervous stimulation or endocrine control. These mechanisms facilitate the adjustment of blood flow and, therefore, perfusion specific to each tissue region. This self-regulation encompasses chemical signals and myogenic controls.
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation.
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation.
Acid-Base Balance
The human body maintains a narrow pH range regulated through acid-base balance. This balance is crucial as changes in the hydrogen ion concentration can disrupt cell membrane stability, alter protein structures, and change enzyme activities. The normal pH of arterial blood is 7.4, venous blood and interstitial fluid is 7.35, and intracellular fluid averages 7.0.
When the pH of arterial blood rises above 7.45, it results in a condition called alkalosis. Conversely, a drop below 7.35 leads to...
When the pH of arterial blood rises above 7.45, it results in a condition called alkalosis. Conversely, a drop below 7.35 leads to...
