Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan.
Gene. 2023 Aug 20;878:147585. doi: 10.1016/j.gene.2023.147585. Epub 2023 Jun 23.
The endocannabinoid system receptors, cannabinoid receptors type-1 (CBR-1) and -2 (CBR-2), are implicated in several behavioral and cognitive processes. Many studies have indicated a correlation between cannabinoid receptors and angiogenesis. The current study aims to reveal the possible molecular signaling involved in brain angiogenesis induced by the activation of CBR-1 and CBR-2. We investigated whether the synthetic cannabinoid XLR-11, an agonist of CBR-1 and CBR-2, influences the mRNA and protein expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (ANG1) and -2 (ANG2) in human brain microvascular endothelial cells (hBMVEs). Furthermore, we determined the phosphorylation of glycogen synthase kinase 3 beta (GSK3B) expression. Treatment of hBMVEs cells with XLR-11 elevated the mRNA levels of VEGF, ANG1, and ANG2. The secretion of these proangiogenic factors was increased in the media. Furthermore, the intracellular expression of VEGF, ANG1, ANG2, and GSK3B was significantly increased. This current research provides a new possible approach by targeting the cannabinoid receptors to control and regulate brain angiogenesis for treating a variety of angiogenesis-related diseases. This could be achived by using different agonists or antagonists of the cannabinoid receptors based on the nature of the diseases.
内源性大麻素系统受体，大麻素受体 1（CBR-1）和 2（CBR-2），参与多种行为和认知过程。许多研究表明大麻素受体与血管生成之间存在相关性。本研究旨在揭示 CBR-1 和 CBR-2 激活诱导脑血管生成中可能涉及的分子信号通路。我们研究了合成大麻素 XLR-11 是否影响血管内皮生长因子（VEGF）、血管生成素 1（ANG1）和 -2（ANG2）在人脑血管内皮细胞（hBMVEs）中的 mRNA 和蛋白表达。此外，我们还测定了糖原合酶激酶 3β（GSK3β）表达的磷酸化水平。XLR-11 处理 hBMVEs 细胞后，VEGF、ANG1 和 ANG2 的 mRNA 水平升高。这些促血管生成因子在培养基中的分泌增加。此外，VEGF、ANG1、ANG2 和 GSK3β 的细胞内表达也显著增加。本研究为通过靶向大麻素受体来控制和调节脑血管生成以治疗各种与血管生成相关的疾病提供了一种新的可能方法。这可以通过使用不同的大麻素受体激动剂或拮抗剂来实现，具体取决于疾病的性质。
