title: HoxA10 and HoxA11 Regulate the Expression of Contraction-Associated Proteins and Contribute to Regionalized Myometrium Phenotypes in Women.
abstract: A relaxed fundus (FUN) and a contracted lower uterine segment (LUS) of human myometrium are required for maintaining pregnancy. How this regional myometrium function is regulated remains unclear. We have previously reported that the homeobox protein A13 (HoxA13) is highly expressed in the LUS and can enhance the expression of contraction-associated proteins (CAPs). Here, we show that in contrast to HoxA13, HoxA10 and HoxA11 genes are expressed at significantly higher levels in myometrium tissues and primary myocytes from the FUN. When introduced exogenously into a human myometrial cell line, HoxA10 and HoxA11 suppress the messenger RNA (mRNA) levels of several CAP genes including interleukin-1 beta (IL-1β), IL-6, connexin 43 (Cx43), and cyclooxygenase 2 (Cox2). Consistently, enhanced HoxA10 and HoxA11 expressions strongly inhibited IL-1β and Cx43 protein levels. We further confirmed that higher expression of HoxA10 and HoxA11 genes in primary myocytes from the FUN compared to that from the LUS was associated with lower expression of IL-1β, IL-6, Cox2, and Cx43 genes. We conclude that the expression patterns of HoxA10, HoxA11, and HoxA13 and their actions in regulating CAP genes in FUN and LUS create regionalized myometrium phenotypes in women that may be important to control regionalized myometrium contractility for maintaining pregnancy.
authors.affiliation: 1 Department of Urologic Sciences, The Vancouver prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1 Department of Urologic Sciences, The Vancouver prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Haolong
authors.initials: H
authors.lastname: Li
authors.affiliation: 1 Department of Urologic Sciences, The Vancouver prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ning
authors.initials: N
authors.lastname: Xie
authors.affiliation: 1 Department of Urologic Sciences, The Vancouver prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ruiqi
authors.initials: R
authors.lastname: Chen
authors.affiliation: 1 Department of Urologic Sciences, The Vancouver prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ahn Rhi
authors.initials: AR
authors.lastname: Lee
authors.affiliation: 2 Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada.
authors.forename: Donna
authors.initials: D
authors.lastname: Slater
authors.affiliation: 3 Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lye
authors.affiliation: 1 Department of Urologic Sciences, The Vancouver prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.|3 Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Xuesen
authors.initials: X
authors.lastname: Dong
mesh_terms: D000328:Adult; D002460:Cell Line; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D009215:Myometrium / Q000378:metabolism*; D010641:Phenotype; D014590:Uterine Contraction / Q000235:genetics / Q000378:metabolism*
chemical_list: D018031:Connexin 43; C484298:HOXA11 protein, human; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; C069634:HOXA10 protein, human; D051546:Cyclooxygenase 2
keywords: HoxA proteins; contraction-associated proteins; myometrium; pregnancy