Human endometrial milk fat globule-epidermal growth factor 8 (MFGE8) is up regulated by estradiol at the transcriptional level, and its secretion via microvesicles is stimulated by human chorionic gonadotropin (hCG)

Handle URI:
http://hdl.handle.net/10754/550813
Title:
Human endometrial milk fat globule-epidermal growth factor 8 (MFGE8) is up regulated by estradiol at the transcriptional level, and its secretion via microvesicles is stimulated by human chorionic gonadotropin (hCG)
Authors:
Sarhan, Abbaa; Bocca, Silvina; Yu, Liang; Anderson, Sandra; Jacot, Terry; Burch, Tanya; Nyalwidhe, Julius O; Sullivan, Claretta; Kaur, Mandeep; Bajic, Vladimir B. ( 0000-0001-5435-4750 ) ; Oehninger, Sergio
Abstract:
Objective: We have recently showed that MFGE8, a novel epithelial cell protein in the human endometrium, upregulated during the window of implantation. We hypothesized that MFGE8 may act as a key modulator of endometrial remodeling and trophoblast invasion. The aims of this study were (i) to investigate the in vitro regulation of human endometrial epithelial cells MFGE8 transcription, translation, and secretion by sex steroids and hCG; and (ii) to examine the possibility of MFGE8 secretion via microvesicles. Design: Experimental in vitro study using Ishikawa cells. Setting: University center. Interventions: Treatment with estradiol (E2), progesterone (P4), and human chorionic gonatropin (hCG). Main outcome measures: MFGE8 mRNA and protein expression, and identification of secreted microvesicles by mass spectrometry (MS) and immunoblotting. Results: E2, but not P4 or hCG, significantly upregulated MFGE8 mRNA expression. hCG significantly increased MFGE8 secretion. Microvesicels obtained after ultracentrifugation were visualized with atomic force microscopy ranging from ~100 to 200 nm. In addition to the expected 46 kD protein, the microvesicles contained a second form of secreted MFGE8 measuring ~30 kD which was confirmed by MS. Conclusions: We demonstrated (i) dual effects of E2 and hCG on the regulation of MFGE8, and (ii) MFGE8 protein secretion in association with microvesicles. MFGE8 has the potential to modulate endometrial function and implantation via exocrine and/ or paracrine-autocrine effects. To the best of our knowledge, this is the first demonstration of microvesicular secretion of any regulatory protein by endometrial epithelial cells, providing initial evidence suggestive of microvesicular participation in cellular trafficking information in the non-pregnant and pregnant endometrium.
KAUST Department:
Computational Bioscience Research Center (CBRC)
Citation:
Human endometrial milk fat globule-epidermal growth factor 8 (MFGE8) is up regulated by estradiol at the transcriptional level, and its secretion via microvesicles is stimulated by human chorionic gonadotropin (hCG) 2013, 1 (1):1 Cell signalling and Trafficking
Publisher:
Herbert Publications Limited (HOAJ)
Journal:
Cell signalling and Trafficking
Issue Date:
17-Oct-2013
DOI:
10.7243/2054-1481-1-1
Type:
Article
ISSN:
2054-1481
Additional Links:
http://www.hoajonline.com/cellsignaltraffic/2054-1481/1/1
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorSarhan, Abbaaen
dc.contributor.authorBocca, Silvinaen
dc.contributor.authorYu, Liangen
dc.contributor.authorAnderson, Sandraen
dc.contributor.authorJacot, Terryen
dc.contributor.authorBurch, Tanyaen
dc.contributor.authorNyalwidhe, Julius Oen
dc.contributor.authorSullivan, Clarettaen
dc.contributor.authorKaur, Mandeepen
dc.contributor.authorBajic, Vladimir B.en
dc.contributor.authorOehninger, Sergioen
dc.date.accessioned2015-04-28T11:29:06Zen
dc.date.available2015-04-28T11:29:06Zen
dc.date.issued2013-10-17en
dc.identifier.citationHuman endometrial milk fat globule-epidermal growth factor 8 (MFGE8) is up regulated by estradiol at the transcriptional level, and its secretion via microvesicles is stimulated by human chorionic gonadotropin (hCG) 2013, 1 (1):1 Cell signalling and Traffickingen
dc.identifier.issn2054-1481en
dc.identifier.doi10.7243/2054-1481-1-1en
dc.identifier.urihttp://hdl.handle.net/10754/550813en
dc.description.abstractObjective: We have recently showed that MFGE8, a novel epithelial cell protein in the human endometrium, upregulated during the window of implantation. We hypothesized that MFGE8 may act as a key modulator of endometrial remodeling and trophoblast invasion. The aims of this study were (i) to investigate the in vitro regulation of human endometrial epithelial cells MFGE8 transcription, translation, and secretion by sex steroids and hCG; and (ii) to examine the possibility of MFGE8 secretion via microvesicles. Design: Experimental in vitro study using Ishikawa cells. Setting: University center. Interventions: Treatment with estradiol (E2), progesterone (P4), and human chorionic gonatropin (hCG). Main outcome measures: MFGE8 mRNA and protein expression, and identification of secreted microvesicles by mass spectrometry (MS) and immunoblotting. Results: E2, but not P4 or hCG, significantly upregulated MFGE8 mRNA expression. hCG significantly increased MFGE8 secretion. Microvesicels obtained after ultracentrifugation were visualized with atomic force microscopy ranging from ~100 to 200 nm. In addition to the expected 46 kD protein, the microvesicles contained a second form of secreted MFGE8 measuring ~30 kD which was confirmed by MS. Conclusions: We demonstrated (i) dual effects of E2 and hCG on the regulation of MFGE8, and (ii) MFGE8 protein secretion in association with microvesicles. MFGE8 has the potential to modulate endometrial function and implantation via exocrine and/ or paracrine-autocrine effects. To the best of our knowledge, this is the first demonstration of microvesicular secretion of any regulatory protein by endometrial epithelial cells, providing initial evidence suggestive of microvesicular participation in cellular trafficking information in the non-pregnant and pregnant endometrium.en
dc.publisherHerbert Publications Limited (HOAJ)en
dc.relation.urlhttp://www.hoajonline.com/cellsignaltraffic/2054-1481/1/1en
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.subjectEndometriumen
dc.subjectgene expressionen
dc.subjectMFGE8en
dc.subjectmicrovesiclesen
dc.titleHuman endometrial milk fat globule-epidermal growth factor 8 (MFGE8) is up regulated by estradiol at the transcriptional level, and its secretion via microvesicles is stimulated by human chorionic gonadotropin (hCG)en
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalCell signalling and Traffickingen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionThe Jones institute for Reproductive Medicine, Department of Obstetrics and Gynecology, USAen
dc.contributor.institutionDepartment of Microbiology and Molecular Cell Biology -Center for Biomedical Proteomics, USAen
dc.contributor.institutionDepartment of Surgery, Eastern Virginia Medical School, Norfolk, Virginia 23507, USAen
dc.contributor.institutionThe Jones institute for Reproductive Medicine, Eastern Virginia Medical School, Department of Obstetrics and Gynecology, USAen
dc.contributor.institutionColumbia Fertility Associates, 2440 M St NW, Suite 401, Washington DC 20037, USAen
kaust.authorKaur, Mandeepen
kaust.authorBajic, Vladimir B.en
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