title: Protein Inhibitor of Activated STAT3 (PIAS3) Is Down-Regulated in Eutopic Endometrium of Women with Endometriosis.
abstract: Endometriosis is a major cause of chronic pelvic pain and infertility. Activation of STAT3 appears central to the inflammatory phenotype of eutopic endometrium in women with endometriosis. However, the molecular mechanism by which this occurs remains unknown. Our objective is to determine how STAT3 activity is regulated in endometriosis. Protein inhibitor of activated STAT3 (PIAS3) is a negative regulator of STAT3 activity. We examined the levels of PIAS3 in endometrium from women with and without endometriosis using Western blot analysis and immunohistochemistry. Levels of PIAS3 are significantly lower, in contrast with phosphorylation of STAT3, in women with endometriosis compared to women without endometriosis. Furthermore, induction of endometriosis in the baboon showed a significant reduction of PIAS3 expression during the progression of the disease. Interferon-γ (INFγ) reduces PIAS3 protein levels and increases phospho-STAT3 levels through CXCL10 in endometrial cells, Ishikawa, and 12Z cells. These results suggest that attenuation of PIAS3 causes aberrant activation of STAT3 in endometriosis, leading to inflammatory changes that may impair fertility or cause pain.
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, Grand Rapids, Michigan.
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Yoo
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, Grand Rapids, Michigan.
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, Grand Rapids, Michigan.
authors.forename: Asgerally T
authors.initials: AT
authors.lastname: Fazleabas
authors.affiliation: Department of Obstetrics and Gynecology, Queens University, Kingston, Canada.
authors.forename: Chandrakant
authors.initials: C
authors.lastname: Tayade
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Young
authors.affiliation: Department of Obstetrics and Gynecology, University of South Carolina School of Medicine, Greenville Health System, Greenville, South Carolina blessey@ghs.org.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Lessey
mesh_terms: D000818:Animals; D018450:Disease Progression; D015536:Down-Regulation; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D010215:Papio; D010766:Phosphorylation; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D050828:Protein Inhibitors of Activated STAT; D050796:STAT3 Transcription Factor; D007371:Interferon-gamma
keywords: PIAS3; STAT3; cytokine; endometriosis; endometrium