Details

Autor(en) / Beteiligte

• Li, Wan‐Ning
• Hsiao, Kuei‐Yang
• Wang, Chu‐An
• Chang, Ning
• Wu, Meng‐Hsing
• Tsai, Shaw‐Jenq Sean

Titel

Repression of COUP‐TFII by proinflammatory cytokines contributes to endometriotic lymphangiogenesis

Ist Teil von

• The FASEB journal, 2019-04, Vol.33 (S1), p.491.4-491.4

Ort / Verlag

The Federation of American Societies for Experimental Biology

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Endometriosis is a common gynecological disease that affects 8–10% women of reproductive age. It is characterized as the presence of endometriotic lesions outside the uterine cavity and causes severe symptoms in patients such as pelvic pains, dyspareunia, and even infertility. Greater angiogenic and lymphangiogenic processes have been found in ectopic lesions. However, the underlying mechanism is largely unknown. In the present study, we found VEGF‐C is highly secreted by endometriotic stromal cells. Bioinformatic and molecular characterization reveals that elevation of VEGF‐C in endometriotic stromal cells is mediated by derepression of chicken ovalbumin upstream promoter‐transcription factor II (COUP‐TFII) dependent transcriptional regulation. Further investigation demonstrates that level of COUP‐TFII is suppressed by proinflammatory cytokines such as interleukin‐1β and tumor necrosis factor‐α. More importantly, we show, for the first time, that functional VEGF‐C can be transported by exosomes, a 30–100 nm‐size extracellular vesicles derived from the endosomal compartments, to enhance the tube formation abilities of lymphatic endothelial cells. Blockage of VEGF‐C signaling by a highly selective inhibitor of VEGFR‐2/3, Lenvatinib, abolishes loss of COUP‐TFII‐mediated lymphangiogenesis in endometriosis both in in vitro and in vivo models. Herein, we unveil the novel mechanism of VEGF‐C transportation by extracellular vesicles to communicate between endometriotic cells and lymphatic endothelial cells and demonstrate the pathophysiological process of VEGF‐C in the progression of endometriosis. This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.