The Role of Anthrax Toxin Receptor-2 in Pathogenesis of Endometriosis

  • 徐 敬庭

Student thesis: Master's Thesis

Abstract

Endometriosis is one of the most common gynecological diseases in women of reproductive age The common symptoms of endometriosis are dysmenorrhea dyspareunia pelvic pain and infertility which reduces life quality of patients Endometriosis is defined as the endometrial tissue present outside of the uterus with an unknown etiology However it is clear that an increase in the adhesion ability should enhance the retrograded endometrial tissues to attach and survive outside the uterus This study was designed to investigate the underlying mechanism responsible for the survival of ectopic endometriotic cells with the focus on adhesion ability Anthrax toxin receptor 2 (ANTXR2) has been known to play a crucial role in angiogenesis and the binding to extracellular matrix Herein we found that ANTXR2 was overexpressed in ectopic endometriotic tissues and purified stromal cells by using real time RT-PCR and Western blotting To test whether ANTXR2 promotes endometriotic lesion attachment and survival at the early stage of endometriosis stromal cells were treated with 1 2 3 4 6 -penta-O-galloyl-β-D-glucopyranose (PGG) an inhibitor of ANTXR2 Results demonstrated that treatment with PGG not only reduced adhesion ability but also inhibited the growth of endometriotic stromal cells We also found that treatment with ANTXR2 inhibitor can decrease phosphorylation of focal adhesion kinase (FAK) and extracellular signal–regulated kinases (ERK) suggesting that ANTXR2 might regulate cell adhesion ability through FAK signaling transduction and regulate cell growth through ERK pathway Next we aimed to characterize how ANXTR2 is regulated during the development of endometriosis Since chronic inflammation is a key feature of endometriosis and the abnormal increase of proinflammatory cytokines such as interleukin 1 beta (IL1-β) tumor necrosis factor alpha (TNF-?) and transforming growth factor-β1 (TGF-β1) in peritoneal fluid secreted by endometriotic lesion had been documented we tested whether peritoneal fluid from patients with endometriosis and also these proinflammatory cytokines in peritoneal fluid can induce ANXTR2 expression Indeed treatment with peritoneal fluid from patients with endometriosis stimulated ANTXR2 expression But only treatment with TNF-? can significantly increase ANTXR2 expression Finally treatment of normal endometrial stromal cells with TNF-? markedly enhanced adhesion ability Taken together our results suggest that ANTXR2 is a critical factor in endometrial physiology and TNF-? might be a driving force to promote the early development of endometriosis via increase ANTXR2 expression
Date of Award2016 Aug 31
Original languageEnglish
SupervisorMeng-Hsing Wu (Supervisor)

Cite this

The Role of Anthrax Toxin Receptor-2 in Pathogenesis of Endometriosis
敬庭, 徐. (Author). 2016 Aug 31

Student thesis: Master's Thesis