Ling Zhang1, Wenqian Xiong1, Na Li1, Hengwei Liu1, Haitang He1, Yu Du1, Zhibing Zhang2, Yi Liu3. 1. Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People's Republic of China. 2. Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia. 3. Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People's Republic of China. Electronic address: Liqun94@163.com.
Abstract
OBJECTIVE: To investigate whether G protein-coupled estrogen receptor (GPER, also known as GPR30 and GPER1) stabilizes hypoxia-inducible factor 1α (HIF-1α) in eutopic endometrium (EuEM) of endometriosis. DESIGN: Immunohistochemical analysis and experimental in vitro study. SETTING: University hospital. PATIENT(S): Patients with or without endometriosis. INTERVENTION(S): The EuEM and normal control endometrium (CoEM) were obtained by curettage. Primary cultured endometrial stromal cells (ESCs) were treated with 17β-E2, G1, or G15. MAIN OUTCOME MEASURE(S): The EuEM and CoEM were collected for immunohistochemistry. Western blot, polymerase chain reaction, ELISA, and dual luciferase experiments were used to detect expression of GPER, HIF-1α, vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP9) in ESCs. Estradiol and G1 were used as agonists of GPER, G15 as an antagonist. Migration of ESCs and endothelial tube formation of human umbilical vein endothelial cells cultured in medium collected from ESCs were measured. RESULT(S): Protein levels of GPER and HIF-1α were higher in EuEM than in CoEM. Protein levels of HIF-1α but not HIF-1α mRNA levels increased concurrently with GPER after E2 and G1 treatment. Furthermore, expression and activity of VEGF and MMP9 increased under E2 and G1 stimulation. However, these effects disappeared when GPER was blocked. CONCLUSION(S): G protein-coupled estrogen receptor stabilizes HIF-1α and thus promotes HIF-1α-induced VEGF and MMP9 in ESCs, which play critical roles in endometriosis.
OBJECTIVE: To investigate whether G protein-coupled estrogen receptor (GPER, also known as GPR30 and GPER1) stabilizes hypoxia-inducible factor 1α (HIF-1α) in eutopic endometrium (EuEM) of endometriosis. DESIGN: Immunohistochemical analysis and experimental in vitro study. SETTING: University hospital. PATIENT(S): Patients with or without endometriosis. INTERVENTION(S): The EuEM and normal control endometrium (CoEM) were obtained by curettage. Primary cultured endometrial stromal cells (ESCs) were treated with 17β-E2, G1, or G15. MAIN OUTCOME MEASURE(S): The EuEM and CoEM were collected for immunohistochemistry. Western blot, polymerase chain reaction, ELISA, and dual luciferase experiments were used to detect expression of GPER, HIF-1α, vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP9) in ESCs. Estradiol and G1 were used as agonists of GPER, G15 as an antagonist. Migration of ESCs and endothelial tube formation of humanumbilical vein endothelial cells cultured in medium collected from ESCs were measured. RESULT(S): Protein levels of GPER and HIF-1α were higher in EuEM than in CoEM. Protein levels of HIF-1α but not HIF-1α mRNA levels increased concurrently with GPER after E2 and G1 treatment. Furthermore, expression and activity of VEGF and MMP9 increased under E2 and G1 stimulation. However, these effects disappeared when GPER was blocked. CONCLUSION(S): G protein-coupled estrogen receptor stabilizes HIF-1α and thus promotes HIF-1α-induced VEGF and MMP9 in ESCs, which play critical roles in endometriosis.
Authors: P Jaakkola; D R Mole; Y M Tian; M I Wilson; J Gielbert; S J Gaskell; A von Kriegsheim; H F Hebestreit; M Mukherji; C J Schofield; P H Maxwell; C W Pugh; P J Ratcliffe Journal: Science Date: 2001-04-05 Impact factor: 47.728
Authors: Ernestina M De Francesco; Federica Sotgia; Robert B Clarke; Michael P Lisanti; Marcello Maggiolini Journal: Int J Mol Sci Date: 2017-12-14 Impact factor: 5.923