Neuroimmune interactions are involved in the development of endometriosis. Here, we examined the role of a neuropeptide, calcitonin gene–related peptide (CGRP), and its receptor, receptor activity–modifying protein (RAMP) 1, in growth of endometrial tissues and the formation of blood and lymphatic vessels in a mouse ectopic endometrial transplantation model. Endometrial fragments from donor wild‐type (WT) mice transplanted into the peritoneal wall of recipient WT mice grew with increased density of blood and lymphatic vessels. When tissues from RAMP1‐deficient (RAMP1^−/−) mice were transplanted into RAMP1^−/− mice, implant growth and angiogenesis/lymphangiogenesis were decreased. CGRP was up‐regulated in dorsal root ganglia, and CGRP⁺ nerve fibres were distributed into the implants from the peritoneum. RAMP1 was co‐expressed with CD11b (macrophages) and S100A4 (fibroblasts), but did not co‐localize with blood vessel endothelial cell marker CD31 or lymphatic vessel endothelial hyaluronan receptor (LYVE)‐1. Cultured with CGRP, macrophages up‐regulated vascular endothelial growth factor (VEGF)‐A, VEGF‐C and VEGF‐D, whereas fibroblasts up‐regulated VEGF‐C, but not VEGF‐A or VEGF‐D, in a RAMP1‐dependent manner. CGRP receptor antagonist CGRP8‐37 inhibited growth of and angiogenesis/lymphangiogenesis within endometrial tissue implants. These results suggest that RAMP1 signalling is crucial for growth and angiogenesis/lymphangiogenesis in endometrial tissue. Blockade of RAMP1 is a potential tool for the treatment of endometriosis.

中文翻译：

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受体活性修饰蛋白1的抑制抑制子宫内膜异位症的发展以及血液和淋巴管的形成。

神经免疫相互作用参与子宫内膜异位症的发展。在这里，我们研究了神经肽降钙素基因相关肽（CGRP）及其受体，受体活性修饰蛋白（RAMP）1在小鼠异位子宫内膜组织的生长以及血液和淋巴管形成中的作用。子宫内膜移植模型。来自野生野生型（WT）小鼠的子宫内膜碎片移植到受体野生型小鼠的腹膜壁中时，其血液和淋巴管密度增加。当将来自缺乏RAMP1的小鼠（RAMP1 ^-/-）的组织移植到RAMP1 ^-/-小鼠中时，植入物的生长和血管生成/淋巴管生成减少了。CGRP在背根神经节上调，而CGRP ⁺神经纤维从腹膜分布到植入物中。RAMP1与CD11b（巨噬细胞）和S100A4（成纤维细胞）共表达，但未与血管内皮细胞标志物CD31或淋巴管内皮透明质酸受体（LYVE）-1共定位。用CGRP培养的巨噬细胞在依赖RAMP1的条件下上调了血管内皮生长因子（VEGF）-A，VEGF-C和VEGF-D，而成纤维细胞上调了VEGF-C，但不上调VEGF-A或VEGF-D。方式。CGRP受体拮抗剂CGRP8-37抑制子宫内膜组织植入物的生长以及血管生成/淋巴管生成。这些结果表明，RAMP1信号对于子宫内膜组织的生长和血管生成/淋巴管生成至关重要。阻断RAMP1是治疗子宫内膜异位症的潜在工具。