| Abstract |
Angiogenesis is a fundamental process in reproduction and wound healing. Angiogenesis is also indispensable for solid tumor growth and metastasis, and also associated with angiogenic diseases. Beta-endorphin (β-EP), derived from its precursor pro-opiomelancortin (POMC), is well known for its role in nociception and immune regulation. However, the function of morphine and β-EP during angiogenesis remains characterization. One previous study indicated that morphine inhibited the proliferation and hypoxia-induced vascular endothelial growth factor (VEGF) release of endothelial cells. Contrastingly, another report found that morphine via Ras/PI3k/MAPK/ERK signaling promotes the survival and angiogenesis in endothelial cells. Besides, endogenous opioid peptides stimulated angiogenesis in chicken allantoic membrane assay through opioid receptors. Thus, the function and mechanism of β-EP and opioid receptors in angiogenesis are controversial. This study evaluated the culture effects of β-EP and morphine on angiogenesis . It was found that β-EP stimulated the proliferation, migration, and tube formation of endothelial cells in a dose-dependent manner. Morphine at a high dose inhibited the proliferation, migration, and tube formation of endothelial cells. In the ex vivo rat aortic ring assay, β-EP enhanced, whereas morphine perturbed, the microvessel sprouting. We also confirmed the expression of MOR，DOR，KOR opioid receptor in endothelial cells. Application of naloxone, a selective opioid antagonist, and neutralizing antibodies of MOR abolished the angiogenic effect of β-EP and morphine. Thus β-EP and morphine exert the pro- and anti-angiogenic effect via MOR, respectively .Besides, β-EP can be regarded as a novel angiogenic factor. |
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