Luo Huanhuan, Zhang Wei, Zeng Wen, Wang Yu, Feng Jianglong, Lan Yinghua, Dong Xian, Liu Ting, Sun Yan, Lu Hongguang
School of Public Health, Guizhou Medical University, Guiyang, Guizhou, China.
Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Commun Biol. 2025 Mar 31;8(1):529. doi: 10.1038/s42003-025-07958-4.
Many rhodopsin-like G-protein-coupled receptors (Rh-GPCRs) are known to either promote or inhibit angiogenesis. Among these, Opsin 4 and Opsin 5 are specifically involved in vascular development within the eye. Opsin 3 (OPN3), another member of Rh-GPCRs, performs a variety of light-dependent and light-independent functions in extraocular tissue. However, its role in endothelial cells and angiogenesis remains unclear. Here, we found that OPN3 knockdown or knockout in zebrafish impairs embryonic angiogenesis and vascular development. Similarly, silencing OPN3 in human umbilical vein endothelial cells (HUVECs) inhibits cellular proliferation, migration, sprouting, and tube formation, while OPN3 overexpression promotes these cellular processes. Moreover, OPN3 regulates angiogenesis in HUVECs through the VEGFR2-AKT pathway, with OPN3 and VEGFR2 co-localizing at the plasma membrane and forming a physical complex. These findings provide new insights into the non-light-dependent functions of OPN3 in angiogenesis, expanding our understanding of its physiological roles and offering potential therapeutic strategies for angiogenesis-related diseases.
已知许多视紫红质样G蛋白偶联受体（Rh-GPCRs）可促进或抑制血管生成。其中，视蛋白4和视蛋白5特别参与眼内血管发育。视蛋白3（OPN3）是Rh-GPCRs的另一个成员，在眼外组织中发挥多种光依赖和非光依赖功能。然而，其在内皮细胞和血管生成中的作用仍不清楚。在这里，我们发现斑马鱼中OPN3的敲低或敲除会损害胚胎血管生成和血管发育。同样，在人脐静脉内皮细胞（HUVECs）中沉默OPN3会抑制细胞增殖、迁移、芽生和管形成，而OPN3的过表达则促进这些细胞过程。此外，OPN3通过VEGFR2-AKT途径调节HUVECs中的血管生成，OPN3和VEGFR2在质膜上共定位并形成物理复合物。这些发现为OPN3在血管生成中的非光依赖功能提供了新的见解，扩展了我们对其生理作用的理解，并为血管生成相关疾病提供了潜在的治疗策略。
