Open AccessOestrogen‐induced angiogenesis promotes adenomyosis by activating the S lug‐ VEGF axis in endometrial epithelial cells
Author(s) -
Huang TzeSing,
Chen YiJen,
Chou TehYing,
Chen ChihYao,
Li HsinYang,
Huang BenShian,
Tsai HsiaoWen,
Lan HsinYi,
Chang ChengHsuan,
Twu NaeFang,
Yen MingShyen,
Wang PengHui,
Chao KuanChong,
Lee ChunChung,
Yang MuhHwa
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12300
Subject(s) - adenomyosis , angiogenesis , myometrium , endometrium , slug , endometriosis , vascular endothelial growth factor , pathogenesis , vascularity , uterus , cancer research , pathology , medicine , biology , endocrinology , vegf receptors
Adenomyosis is an oestrogen‐dependent disease characterized by the invasion of endometrial epithelial cells into the myometrium of uterus, and angiogenesis is thought to be required for the implantation of endometrial glandular tissues during the adenomyotic pathogenesis. In this study, we demonstrate that compared with eutopic endometria, adenomyotic lesions exhibited increased vascularity as detected by sonography. Microscopically, the lesions also exhibited an oestrogen‐associated elevation of microvascular density and VEGF expression in endometrial epithelial cells. We previously reported that oestrogen‐induced S lug expression was critical for endometrial epithelial–mesenchymal transition and development of adenomyosis. Our present studies demonstrated that estradiol (E2) elicited a S lug‐ VEGF axis in endometrial epithelial cells, and also induced pro‐angiogenic activity in vascular endothelial cells. The antagonizing agents against E2 or VEGF suppressed endothelial cells migration and tubal formation. Animal experiments furthermore confirmed that blockage of E2 or VEGF was efficient to attenuate the implantation of adenomyotic lesions. These results highlight the importance of oestrogen‐induced angiogenesis in adenomyosis development and provide a potential strategy for treating adenomyosis through intercepting the E2‐ S lug‐ VEGF pathway.