Yukai Liu1, Mingqing Li1,2,3, Chunyan Wei1, Lingli Tang1, Yanran Sheng1, Yuyin Liu1, Dajin Li1, Ding Ding1, Jianping Qiu4, Xiaoyong Zhu1,2,3. 1. Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai, China. 2. Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, Fudan University, Shanghai, China. 3. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China. 4. Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
Abstract
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.
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 endometriosispatients. 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.
Authors: Ashley F George; Sushmita Sen; Alexis J Combes; Linda C Giudice; Júlia Vallvé-Juanico; Reuben Thomas; Min-Gyoung Shin; Divyashree Kushnoor; Joshua J Vásquez; Kim Chi Vo; Juan C Irwin; Nadia R Roan Journal: BMC Med Date: 2022-04-15 Impact factor: 11.150