PROBLEM To explore whether the thrombospondin-1(TSP1)-CD47-signal regulatory protein alpha (SIRPα) 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 SIRPα expression on macrophages, which may further exhaust their phagocytic ability. Phagocytosis efficiency of macrophages on EESCs significantly improves by blocking CD47-SIRPα pathway. CONCLUSION TSP1-CD47-SIRPα 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.

中文翻译：

---

TSP1-CD47-SIRPα信号传导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。

问题探讨血小板反应蛋白-1（TSP1）-CD47信号调节蛋白α（SIRPα）信号通路是否对子宫内膜异位症的发展有影响。研究方法子宫内膜基质细胞（ESCs）源自异位和异位子宫内膜组织，伴有或不伴有子宫内膜异位。从有或没有子宫内膜异位的外周血和腹膜液中分离出单核细胞（巨噬细胞）。通过流式细胞术（FCM），免疫组织化学（IHC）和RT-qPCR研究了分子的表达水平。通过ELISA评估TSP1的浓度。血管生成和吞噬能力分别通过试管形成测定和吞噬测定来测量。结果我们证实子宫内膜异位症患者通路中关键分子的上调。TSP1可以促进正常ESC（NESC）的生长和纤维化。它同时促进炎性因子的分泌并抑制巨噬细胞的吞噬能力。此外，TSP1可改善血管内皮细胞（VEC）的增殖。这些作用可能被CD47阻断抗体所抵消。另外，异位ESC（EESC）直接改善巨噬细胞上SIRPα的表达，这可能会进一步耗尽其吞噬能力。通过阻止CD47-SIRPα途径，巨噬细胞在EESC上的吞噬效率显着提高。结论TSP1-CD47-SIRPα信号通路不仅可以提高NESC自身的生存能力，还可以通过影响巨噬细胞和VEC的功能来促进NESC的生存环境，它们相互促进，共同促进子宫内膜异位症的发展。它同时促进炎性因子的分泌并抑制巨噬细胞的吞噬能力。此外，TSP1可改善血管内皮细胞（VEC）的增殖。这些作用可能被CD47阻断抗体所抵消。另外，异位ESC（EESC）直接改善巨噬细胞上SIRPα的表达，这可能会进一步耗尽其吞噬能力。通过阻止CD47-SIRPα途径，巨噬细胞在EESC上的吞噬效率显着提高。结论TSP1-CD47-SIRPα信号通路不仅可以提高NESC自身的生存能力，还可以通过影响巨噬细胞和VEC的功能来促进NESC的生存环境，它们相互促进，共同促进子宫内膜异位症的发展。它同时促进炎性因子的分泌并抑制巨噬细胞的吞噬能力。此外，TSP1可改善血管内皮细胞（VEC）的增殖。这些作用可能被CD47阻断抗体所抵消。另外，异位ESC（EESC）直接改善巨噬细胞上SIRPα的表达，这可能会进一步耗尽其吞噬能力。通过阻止CD47-SIRPα途径，巨噬细胞在EESC上的吞噬效率显着提高。结论TSP1-CD47-SIRPα信号通路不仅可以提高NESC本身的生存能力，而且还可以通过影响巨噬细胞和VEC的功能来促进其生存环境，而巨噬细胞和VEC的作用是相互促进并共同促进子宫内膜异位症的发展。