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TSP1‐CD47‐SIRPα signaling facilitates the development of endometriosis by mediating the survival of ectopic endometrium
Author(s) -
Liu Yukai,
Li Mingqing,
Wei Chunyan,
Tang Lingli,
Sheng Yanran,
Liu Yuyin,
Li Dajin,
Ding Ding,
Qiu Jianping,
Zhu Xiaoyong
Publication year - 2020
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.13236
Subject(s) - cd47 , endometriosis , stromal cell , angiogenesis , phagocytosis , flow cytometry , microbiology and biotechnology , biology , cancer research , immunology , medicine
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.