Suppression of COUP-TFII by Proinflammatory Cytokines Contributes to the Pathogenesis of Endometriosis

Abstract

Because overexpression of COX-2 has been demonstrated to be a master regulator in endometriosis progression, our data demonstrate the critical function of proinflammatory cytokines and the COUP-TFII regulatory gene network in the progression of endometriosis.

Targeting hypoxia-mediated YAP1 nuclear translocation ameliorates pathogenesis of endometriosis without compromising maternal fertility

“…Ectopic stromal cells have been demonstrated to exert a higher capability of steroidogenesis via increasing StAR expression [35], mainly induced by COX-2-derived PGE 2 [36]. In addition, both IL-1β and DUSP-2 regulate COX-2 expression and thus control angiogenesis via inducing the expression of VEGF-C and IL-8 [14,[37][38][39], and suppress the immune response via down-regulation of the phagocytic ability of macrophages [40][41][42]. These results provide a broad explanation of how ectopic endometrial tissues can evade immune clearance, increase cell attachment and implantation, prevent apoptosis when ovarian oestrogen is not available, and proliferate in the hostile microenvironment.…”

Endometriosis and possible inflammation markers

“…Downregulation of COUP-TFII in endometriotic stromal cells mediated by proinflammatory cytokines including IL-1b, TNF-a, and transforming growth factor (TGF)-b1 via microRNA-302a results in COX-2 upregulation. 8 These promote an inflammatory microenvironment for the development of endometriosis.…”

Epigenetic regulation of the pathological process in endometriosis

“…The miR‐20a‐mediated hypoxia‐inhibited DUSP2 prolongs the phosphorylation of ERK‐1 and ‐2, which further augments the PGE 2 signaling and thus potentiates PGE 2 ‐induced gene expression (Figures and ). In contrast, the biosynthesis of PGE 2 also is stimulated through a miRNA‐mediated positive feedback loop . Chicken ovalbumin upstream promoter (COUP)‐transcription factor (TF)II, which binds the COX‐2 promoter region and elevates the expression of COX‐2 in the eutopic endometrium, is suppressed by inflammatory stimuli from the peritoneal fluid.…”

“…In contrast, the biosynthesis of PGE 2 also is stimulated through a miRNA-mediated positive feedback loop. 42 Chicken ovalbumin upstream promoter (COUP)-transcription factor (TF)II, which binds the COX-2 promoter region and elevates the expression of COX-2 in the eutopic endometrium, is suppressed by inflammatory stimuli from the peritoneal fluid. Treatment with IL-1β, TNFα, or transforming growth factor β suppresses the expression of COUP-TFII through miR-302a binding to its 3′-untranslated region (UTR).…”