Morohoshi Kazunori, Mochinaga Ryo, Watanabe Tsukasa, Nakajima Ryojun, Harigaya Toshio
Department of Life SciencesLaboratory of Functional Anatomy, Faculty of Agriculture, Meiji University, Kawasaki, Japan
Department of Life SciencesLaboratory of Functional Anatomy, Faculty of Agriculture, Meiji University, Kawasaki, Japan.
Endocr Connect. 2018 May;7(5):630-636. doi: 10.1530/EC-18-0116. Epub 2018 Apr 5.
Many functions of vasoinhibins have been reported, but its receptor has not been clarified yet. Vasoinhibins, 11-18 kDa N-terminal fragments of prolactin, have anti-angiogenic activity and act on endothelial cells to induce apoptosis and to inhibit migration and proliferation, which are opposite to the effects of prolactin. Although vasoinhibins bind to the prolactin receptor, its binding activity is very weak compared to prolactin. Therefore, in this study, we evaluated the binding activity between 16 kDa vasoinhibin and integrin beta1, alpha5 beta1, alpha1 beta1 and alphaV beta3 to identify a specific receptor for vasoinhibins. Moreover, we examined whether 16 kDa vasoinhibin induced apoptosis through integrin beta1 and alpha5 beta1 in endothelial cells. In this study, binding assays and co-immunoprecipitation experiments demonstrated that 16 kDa vasoinhibin could bind strongly to integrin beta1 and alpha5 beta1. Moreover, neutralizing with integrin beta1 and alpha5 beta1 antibody could inhibit 16 kDa vasoinhibin-induced apoptosis in endothelial cells. These findings suggest that vasoinhibins can act on endothelial cells through integrin alpha5 beta1 to induce apoptosis.
血管抑制素的许多功能已见报道，但其受体尚未明确。血管抑制素是催乳素11 - 18 kDa的N端片段，具有抗血管生成活性，作用于内皮细胞可诱导凋亡并抑制迁移和增殖，这与催乳素的作用相反。虽然血管抑制素可与催乳素受体结合，但其结合活性与催乳素相比非常弱。因此，在本研究中，我们评估了16 kDa血管抑制素与整合素β1、α5β1、α1β1和αVβ3之间的结合活性，以确定血管抑制素的特异性受体。此外，我们检测了16 kDa血管抑制素是否通过内皮细胞中的整合素β1和α5β1诱导凋亡。在本研究中，结合试验和免疫共沉淀实验表明，16 kDa血管抑制素可与整合素β1和α5β1强烈结合。此外，用整合素β1和α5β1抗体中和可抑制16 kDa血管抑制素诱导的内皮细胞凋亡。这些发现提示血管抑制素可通过整合素α5β1作用于内皮细胞以诱导凋亡。
