title: Estrogen Receptor β 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) β levels, enhanced ERβ activity was detected in endometriotic tissues, and the inhibition of enhanced ERβ activity by an ERβ-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ERβ function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ERβ interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNF-α-induced apoptosis. ERβ also interacts with components of the cytoplasmic inflammasome to increase interleukin-1β and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ERβ 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 ERβ function.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Han
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Alkek Center for Molecular Discovery, Verna and Marrs McLean, Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: San-Pin
authors.initials: SP
authors.lastname: Wu
authors.affiliation: Departments of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Hawkins
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Park
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University, School of Medical Science, Ishikawa 920-8640, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kyo
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Alkek Center for Molecular Discovery, Verna and Marrs McLean, Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Sophia Y
authors.initials: SY
authors.lastname: Tsai
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Tsai
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: DeMayo
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: berto@bcm.edu.
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
mesh_terms: D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D049109:Cell Proliferation; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D006801:Humans; D007157:Immunologic Surveillance; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008598:Menstruation / Q000378:metabolism*; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D058847:Inflammasomes; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha