HMGB1对子宫内膜异位症新生血管生成的潜在作用

新生血管生成是子宫内膜异位症（EMs）的重要发病机制之一。异常的血管增生为异位内膜组织的生长、浸润和转移提供有利的条件。高迁移率族蛋白B1（HMGB1）除了介导炎症反应外，近年研究发现其也可促进多种肿瘤的新生血管生成。研究发现，EMs患者体内HMGB1的表达明显升高，提示HMGB1可能参与EMs的发病机制。HMGB1可直接作用于血管内皮细胞，或激活巨噬细胞上调核因子κB（NF-κB），促进血管内皮生长因子（VEGF）的合成和分泌，间接作用于内皮细胞，促进新生血管网的形成。此外，HMGB1还可通过上调成纤维细胞生长因子（FGF）的表达及提高整合素的活性和亲和力，促进内皮细胞的增殖和迁移；刺激血小板衍生生长因子（PDGF）的分泌，募集周细胞和平滑肌细胞，促进血管管状结构的形成；促进内皮细胞释放转录生长因子β（TGF-β），推动血管管状结构的成熟。综述HMGB1参与调节EMs中新生血管生成的潜在作用机制，可为EMs的治疗提供新的靶点。

Potential Role of HMGB1 in Angiogenesis of Endometriosis

Angiogenesis is one of the important pathogenesis of endometriosis. Abnormal neovascularization in endometriosis promotes the proliferation, infiltration and migration of ectopic endometrial cells. High mobility group box 1 protein (HMGB1), as an important pro-inflammatory factor, is recently proved to contribute to angiogenesis in different tumors. HMGB1 can promote neoangiogenesis by acting directly on endothelial cells or indirect effects on endothelial cells by vascular endothelial growth factor (VEGF), which is synthesized and secreted by NF-κB-activating macrophages. In addition, HMGB1 also promotes proliferation and migration of endothelial cells by up-regulating the expression of fibroblast growth factor (FGF) and enhancing the activity as well as the affinity of integrins, promotes the secretion of platelet-derived growth factor (PDGF) and then recruits pericytes and smooth muscle cells, activating the formation of vascular tubular structure. Activates the secretion of TGF-βfrom endothelial cells, finally promoting the maturation of vascular network. Here we review the potential mechanism of HMGB1 underlying the influence of pro-angiogenesis in endometriosis in detail, thus providing a new therapeutic target for endometriosis.