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Augmented epithelial multidrug resistance-associated protein 4 expression in peritoneal endometriosis: regulation by lipoxin A(4).
- Source :
-
Fertility and sterility [Fertil Steril] 2013 Jun; Vol. 99 (7), pp. 1965-73.e2. Date of Electronic Publication: 2013 Mar 06. - Publication Year :
- 2013
-
Abstract
- Objective: To compare the expression of the prostaglandin (PG) E(2) transporter multidrug resistance-associated protein 4 (MRP4) in eutopic and ectopic endometrial tissue from endometriosis patients with that of control subjects and to examine whether MRP4 is regulated by the antiinflammatory lipid lipoxin A(4) (LXA(4)) in endometriotic epithelial cells.<br />Design: Molecular analysis in human samples and a cell line.<br />Setting: Two university hospitals and a private clinic.<br />Patient(s): A total of 59 endometriosis patients and 32 age- and body mass index-matched control subjects undergoing laparoscopy or hysterectomy.<br />Intervention(s): Normal, eutopic, and ectopic endometrial biopsies as well as peritoneal fluid were obtained during surgery performed during the proliferative phase of the menstrual cycle. 12Z endometriotic epithelial cells were used for in vitro mechanistic studies.<br />Main Outcome Measure(s): Tissue MRP4 mRNA levels were quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and localization was analyzed with the use of immunohistochemistry. Cellular MRP4 mRNA and protein were quantified by qRT-PCR and Western blot, respectively. PGE(2) was measured in peritoneal fluid and cell supernatants using an enzyme immunoassay (EIA).<br />Result(s): MRP4 was expressed in eutopic and ectopic endometrium, where it was overexpressed in peritoneal lesions and localized in the cytoplasm of glandular epithelial cells. LXA(4) attenuated MRP4 mRNA and protein levels in endometriotic epithelial cells in a dose-dependent manner, while not affecting the expression of enzymes involved in PGE(2) metabolism. Investigations employing receptor antagonists and small interfering RNA revealed that this occurred through estrogen receptor α. Accordingly, LXA(4) treatment inhibited extracellular PGE(2) release.<br />Conclusion(s): We report for the first time that MRP4 is expressed in human endometrium, elevated in peritoneal endometriosis, and modulated by LXA(4) in endometriotic epithelial cells.<br /> (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Ascitic Fluid metabolism
Biopsy
Blotting, Western
Case-Control Studies
Cell Line
Dinoprostone metabolism
Endometriosis genetics
Endometriosis surgery
Endometrium drug effects
Endometrium surgery
Epithelial Cells drug effects
Estrogen Antagonists pharmacology
Estrogen Receptor alpha antagonists & inhibitors
Estrogen Receptor alpha genetics
Estrogen Receptor alpha metabolism
Female
Humans
Hysterectomy
Immunoenzyme Techniques
Immunohistochemistry
Laparoscopy
Middle Aged
Multidrug Resistance-Associated Proteins genetics
Peritoneal Diseases genetics
Peritoneal Diseases surgery
RNA Interference
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Up-Regulation
Young Adult
Endometriosis metabolism
Endometrium metabolism
Epithelial Cells metabolism
Lipoxins metabolism
Multidrug Resistance-Associated Proteins metabolism
Peritoneal Diseases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1556-5653
- Volume :
- 99
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Fertility and sterility
- Publication Type :
- Academic Journal
- Accession number :
- 23472950
- Full Text :
- https://doi.org/10.1016/j.fertnstert.2013.01.146