TSP1-CD47-SIRPα signaling facilitates the development of endometriosis by mediating the survival of ectopic endometrium
TSP1-CD47-SIRPα signaling facilitates the development of endometriosis by mediating the survival of ectopic endometrium
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TSP1-CD47-SIRPα 信号通过介导异位子宫内膜的存活促进子宫内膜异位症的发展
DOI：
10.1111/aji.13236
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发表时间：
2020-04-18
影响因子：
3.6
通讯作者：
Zhu, Xiaoyong
中科院分区：
文献类型：
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作者：
Liu, Yukai;Li, Mingqing;Zhu, Xiaoyong
目的探讨血小板反应蛋白-1（TSP 1）-CD 47-信号调节蛋白α（SIRP α）信号通路是否对子宫内膜异位症的发生、发展有影响。单核细胞（巨噬细胞）分离自外周血和腹膜液有或没有子宫内膜异位症。通过流式细胞术（FCM）、免疫组织化学（IHC）和RT-qPCR研究分子的表达水平。通过ELISA评估TSP 1的浓度。血管生成和吞噬功能的能力分别通过管形成assay和吞噬assay，respectively.Results我们证实了在子宫内膜异位症患者的通路中的关键分子的上调。TSP 1可以促进正常ESC（NESC）的生长和纤维化。它同时促进炎症因子的分泌和抑制巨噬细胞的吞噬能力。此外，TSP 1可促进血管内皮细胞（VECs）的增殖。这些作用可能被CD 47阻断抗体抵消。此外，异位ESC（EESC）直接改善巨噬细胞上的SIRP α表达，这可能进一步耗尽它们的吞噬能力。结论TSP 1-CD 47-SIRP α信号通路通过影响巨噬细胞和血管内皮细胞的功能，不仅提高了NESC自身的活力，而且改善了其生存环境，二者相互促进，共同促进了子宫内膜异位症的发生发展。
Problem To explore whether the thrombospondin-1(TSP1)-CD47-signal regulatory protein alpha (SIRP alpha) signaling pathway has impacts on the development of endometriosis.Method of study Endometrial stromal cells (ESCs) originated from ectopic and eutopic endometrial tissues with or without endometriosis. Monocytes (Macrophages) were isolated from peripheral blood and peritoneal fluids with or without endometriosis. The expression levels of molecules were investigated by flow cytometry (FCM), immunohistochemistry (IHC), and RT-qPCR. The concentration of TSP1 was assessed via ELISA. The capacities of angiogenesis and phagocytosis were measured via tube formation assay and phagocytic assay, respectively.Results We confirmed the up-regulation of critical molecules within the pathway in endometriosis patients. TSP1 can encourage normal ESCs (NESCs) growth and fibrosis. It simultaneously promotes the secretion of inflammatory factors and inhibits the phagocytic abilities of macrophages. Moreover, the proliferation of vascular endothelial cells (VECs) may be improved by TSP1. These effects may be offset by CD47 blocking antibodies. In addition, ectopic ESCs (EESCs) directly improve SIRP alpha expression on macrophages, which may further exhaust their phagocytic ability. Phagocytosis efficiency of macrophages on EESCs significantly improves by blocking CD47-SIRP alpha pathway.Conclusion TSP1-CD47-SIRP alpha signaling pathway not only improves the viability of NESCs per se but also promotes their survival circumstances by affecting the function of macrophages and VECs, which are mutually reinforcing and jointly promote the development of endometriosis.