Estrogen Receptor ? Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis.

ABSTRACT: Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER) ? levels, enhanced ER? activity was detected in endometriotic tissues, and the inhibition of enhanced ER? activity by an ER?-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ER? function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ER? interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNF-?-induced apoptosis. ER? also interacts with components of the cytoplasmic inflammasome to increase interleukin-1? and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ER? function enhances epithelial-mesenchymal transition signaling, thereby increasing the invasion activity of endometriotic tissues for establishment of ectopic lesions. Collectively, we reveal how endometrial tissue generated by retrograde menstruation can escape immune surveillance and develop into sustained ectopic lesions via gain of ER? function.

SUBMITTER: Han SJ 

PROVIDER: S-EPMC4640214 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature