Involvement of Membrane GRP78 in Trophoblastic Cell Fusion

Glucose-regulated protein 78 (GRP78) is highly expressed in first trimester cytrophoblastic cells (CTBs), especially in syncytiotrophoblast (STB). However, the role of GRP78 in these cells has never been investigated. In this study, we have examined the role of GRP78 in trophoblast fusion using the...

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Vydáno v:PloS one Ročník 7; číslo 8; s. e40596
Hlavní autoři: Fradet, Sarah, Pierredon, Sandra, Ribaux, Pascale, Epiney, Manuella, Shin Ya, Kazuo, Irion, Olivier, Cohen, Marie
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 09.08.2012
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ISSN:1932-6203, 1932-6203
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Abstract Glucose-regulated protein 78 (GRP78) is highly expressed in first trimester cytrophoblastic cells (CTBs), especially in syncytiotrophoblast (STB). However, the role of GRP78 in these cells has never been investigated. In this study, we have examined the role of GRP78 in trophoblast fusion using the Bewo choriocarcinoma cell line as a model of cytotrophoblast fusion. Down regulation of GRP78 by siRNA or chemical inhibitors and use of antibodies against GRP78 in culture medium significantly decreased forskolin-induced fusion capacity of Bewo cells suggesting the involvement of membrane GRP78 in trophoblast fusion. GRP78 expression was also studied in preeclamptic (PE) CTBs which are known to have lower fusion capacity compared to control CTBs. Interestingly, despite the increase of GRP78 mRNA in PE CTBs, membrane GRP78 is significantly decreased in PE CTBs compared to control CTBs, suggesting that relocation of GRP78 from the endoplasmic reticulum to cell surface is probably altered in PE CTBs. Our results imply that membrane GRP78 could play an important role in syncytialisation. They also suggest that deregulation of GRP78 expression or relocation at cell surface might be involved in pregnancy complication associated with defective syncytialisation, such as preeclampsia.
AbstractList Glucose-regulated protein 78 (GRP78) is highly expressed in first trimester cytrophoblastic cells (CTBs), especially in syncytiotrophoblast (STB). However, the role of GRP78 in these cells has never been investigated.BACKGROUNDGlucose-regulated protein 78 (GRP78) is highly expressed in first trimester cytrophoblastic cells (CTBs), especially in syncytiotrophoblast (STB). However, the role of GRP78 in these cells has never been investigated.In this study, we have examined the role of GRP78 in trophoblast fusion using the Bewo choriocarcinoma cell line as a model of cytotrophoblast fusion. Down regulation of GRP78 by siRNA or chemical inhibitors and use of antibodies against GRP78 in culture medium significantly decreased forskolin-induced fusion capacity of Bewo cells suggesting the involvement of membrane GRP78 in trophoblast fusion. GRP78 expression was also studied in preeclamptic (PE) CTBs which are known to have lower fusion capacity compared to control CTBs. Interestingly, despite the increase of GRP78 mRNA in PE CTBs, membrane GRP78 is significantly decreased in PE CTBs compared to control CTBs, suggesting that relocation of GRP78 from the endoplasmic reticulum to cell surface is probably altered in PE CTBs.METHODOLOGY/PRINCIPAL FINDINGSIn this study, we have examined the role of GRP78 in trophoblast fusion using the Bewo choriocarcinoma cell line as a model of cytotrophoblast fusion. Down regulation of GRP78 by siRNA or chemical inhibitors and use of antibodies against GRP78 in culture medium significantly decreased forskolin-induced fusion capacity of Bewo cells suggesting the involvement of membrane GRP78 in trophoblast fusion. GRP78 expression was also studied in preeclamptic (PE) CTBs which are known to have lower fusion capacity compared to control CTBs. Interestingly, despite the increase of GRP78 mRNA in PE CTBs, membrane GRP78 is significantly decreased in PE CTBs compared to control CTBs, suggesting that relocation of GRP78 from the endoplasmic reticulum to cell surface is probably altered in PE CTBs.Our results imply that membrane GRP78 could play an important role in syncytialisation. They also suggest that deregulation of GRP78 expression or relocation at cell surface might be involved in pregnancy complication associated with defective syncytialisation, such as preeclampsia.CONCLUSIONSOur results imply that membrane GRP78 could play an important role in syncytialisation. They also suggest that deregulation of GRP78 expression or relocation at cell surface might be involved in pregnancy complication associated with defective syncytialisation, such as preeclampsia.
Glucose-regulated protein 78 (GRP78) is highly expressed in first trimester cytrophoblastic cells (CTBs), especially in syncytiotrophoblast (STB). However, the role of GRP78 in these cells has never been investigated. In this study, we have examined the role of GRP78 in trophoblast fusion using the Bewo choriocarcinoma cell line as a model of cytotrophoblast fusion. Down regulation of GRP78 by siRNA or chemical inhibitors and use of antibodies against GRP78 in culture medium significantly decreased forskolin-induced fusion capacity of Bewo cells suggesting the involvement of membrane GRP78 in trophoblast fusion. GRP78 expression was also studied in preeclamptic (PE) CTBs which are known to have lower fusion capacity compared to control CTBs. Interestingly, despite the increase of GRP78 mRNA in PE CTBs, membrane GRP78 is significantly decreased in PE CTBs compared to control CTBs, suggesting that relocation of GRP78 from the endoplasmic reticulum to cell surface is probably altered in PE CTBs. Our results imply that membrane GRP78 could play an important role in syncytialisation. They also suggest that deregulation of GRP78 expression or relocation at cell surface might be involved in pregnancy complication associated with defective syncytialisation, such as preeclampsia.
Background Glucose-regulated protein 78 (GRP78) is highly expressed in first trimester cytrophoblastic cells (CTBs), especially in syncytiotrophoblast (STB). However, the role of GRP78 in these cells has never been investigated. Methodology/Principal Findings In this study, we have examined the role of GRP78 in trophoblast fusion using the Bewo choriocarcinoma cell line as a model of cytotrophoblast fusion. Down regulation of GRP78 by siRNA or chemical inhibitors and use of antibodies against GRP78 in culture medium significantly decreased forskolin-induced fusion capacity of Bewo cells suggesting the involvement of membrane GRP78 in trophoblast fusion. GRP78 expression was also studied in preeclamptic (PE) CTBs which are known to have lower fusion capacity compared to control CTBs. Interestingly, despite the increase of GRP78 mRNA in PE CTBs, membrane GRP78 is significantly decreased in PE CTBs compared to control CTBs, suggesting that relocation of GRP78 from the endoplasmic reticulum to cell surface is probably altered in PE CTBs. Conclusions Our results imply that membrane GRP78 could play an important role in syncytialisation. They also suggest that deregulation of GRP78 expression or relocation at cell surface might be involved in pregnancy complication associated with defective syncytialisation, such as preeclampsia.
Background Glucose-regulated protein 78 (GRP78) is highly expressed in first trimester cytrophoblastic cells (CTBs), especially in syncytiotrophoblast (STB). However, the role of GRP78 in these cells has never been investigated. Methodology/Principal Findings In this study, we have examined the role of GRP78 in trophoblast fusion using the Bewo choriocarcinoma cell line as a model of cytotrophoblast fusion. Down regulation of GRP78 by siRNA or chemical inhibitors and use of antibodies against GRP78 in culture medium significantly decreased forskolin-induced fusion capacity of Bewo cells suggesting the involvement of membrane GRP78 in trophoblast fusion. GRP78 expression was also studied in preeclamptic (PE) CTBs which are known to have lower fusion capacity compared to control CTBs. Interestingly, despite the increase of GRP78 mRNA in PE CTBs, membrane GRP78 is significantly decreased in PE CTBs compared to control CTBs, suggesting that relocation of GRP78 from the endoplasmic reticulum to cell surface is probably altered in PE CTBs. Conclusions Our results imply that membrane GRP78 could play an important role in syncytialisation. They also suggest that deregulation of GRP78 expression or relocation at cell surface might be involved in pregnancy complication associated with defective syncytialisation, such as preeclampsia.
Glucose-regulated protein 78 (GRP78) is highly expressed in first trimester cytrophoblastic cells (CTBs), especially in syncytiotrophoblast (STB). However, the role of GRP78 in these cells has never been investigated. In this study, we have examined the role of GRP78 in trophoblast fusion using the Bewo choriocarcinoma cell line as a model of cytotrophoblast fusion. Down regulation of GRP78 by siRNA or chemical inhibitors and use of antibodies against GRP78 in culture medium significantly decreased forskolin-induced fusion capacity of Bewo cells suggesting the involvement of membrane GRP78 in trophoblast fusion. GRP78 expression was also studied in preeclamptic (PE) CTBs which are known to have lower fusion capacity compared to control CTBs. Interestingly, despite the increase of GRP78 mRNA in PE CTBs, membrane GRP78 is significantly decreased in PE CTBs compared to control CTBs, suggesting that relocation of GRP78 from the endoplasmic reticulum to cell surface is probably altered in PE CTBs. Our results imply that membrane GRP78 could play an important role in syncytialisation. They also suggest that deregulation of GRP78 expression or relocation at cell surface might be involved in pregnancy complication associated with defective syncytialisation, such as preeclampsia.
Audience Academic
Author Ribaux, Pascale
Irion, Olivier
Epiney, Manuella
Fradet, Sarah
Shin Ya, Kazuo
Cohen, Marie
Pierredon, Sandra
AuthorAffiliation 1 Department of Gynecology Obstetrics, Faculty of Medicine, Geneva, Switzerland
2 Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan
VU University Medical Center, The Netherlands
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– name: 1 Department of Gynecology Obstetrics, Faculty of Medicine, Geneva, Switzerland
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/22912664$$D View this record in MEDLINE/PubMed
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Conceived and designed the experiments: SF SP PR MC. Performed the experiments: SF SP PR MC. Analyzed the data: SF SP PR MC. Contributed reagents/materials/analysis tools: SF MC. Wrote the paper: SF SP PR MC ME KS OI.
Competing Interests: The authors have declared that no competing interests exist.
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References_xml – reference: 17068222 - Hum Reprod Update. 2007 Mar-Apr;13(2):121-41
– reference: 1838791 - Mol Endocrinol. 1991 Dec;5(12):1862-72
– reference: 9363258 - Early Pregnancy. 1995 Dec;1(4):263-9
– reference: 8547487 - Biol Reprod. 1995 Oct;53(4):905-10
– reference: 16861902 - Cancer Biol Ther. 2006 Jul;5(7):741-4
– reference: 15699139 - J Immunol. 2005 Feb 15;174(4):2092-7
– reference: 19601892 - Mini Rev Med Chem. 2009 Jul;9(8):962-73
– reference: 15081634 - Placenta. 2004 May;25(5):396-407
– reference: 12676351 - Biochim Biophys Acta. 2003 Apr 7;1640(1):25-31
– reference: 15381142 - Int J Biochem Cell Biol. 2005 Jan;37(1):1-16
– reference: 20663796 - Hum Reprod. 2010 Sep;25(9):2229-38
– reference: 16210392 - Hum Reprod. 2006 Jan;21(1):193-201
– reference: 7679981 - Endocrinology. 1993 Mar;132(3):1387-95
– reference: 19632185 - Cell. 2009 Jul 23;138(2):377-88
– reference: 15339968 - J Natl Cancer Inst. 2004 Sep 1;96(17):1300-10
– reference: 16129952 - Chem Immunol Allergy. 2005;89:49-61
– reference: 17546632 - Mol Reprod Dev. 2008 Jan;75(1):175-83
– reference: 20017148 - Proteomics. 2009 Dec;9(23):5316-27
– reference: 16472112 - Curr Mol Med. 2006 Feb;6(1):45-54
– reference: 15837062 - Placenta. 2005 Apr;26 Suppl A:S21-30
– reference: 21309747 - Biochem J. 2011 Mar 1;434(2):181-8
– reference: 21493955 - Reprod Sci. 2011 Nov;18(11):1085-91
– reference: 12757936 - Biochim Biophys Acta. 2003 May 20;1638(1):63-71
– reference: 19823030 - Cancer Biol Ther. 2009 Nov;8(22):2103-5
– reference: 21035520 - Mol Cell Endocrinol. 2011 Jan 30;332(1-2):213-20
– reference: 10693809 - Nature. 2000 Feb 17;403(6771):785-9
– reference: 19151922 - Cell Mol Life Sci. 2009 May;66(9):1556-69
– reference: 2153559 - Exp Cell Res. 1990 Feb;186(2):306-16
– reference: 15890698 - J Physiol. 2005 Jul 15;566(Pt 2):409-23
– reference: 19482905 - Mol Hum Reprod. 2009 Sep;15(9):569-74
– reference: 20208072 - J Biol Chem. 2010 May 14;285(20):15065-75
– reference: 9852131 - J Biol Chem. 1998 Dec 18;273(51):34594-602
– reference: 19331544 - Antioxid Redox Signal. 2009 Sep;11(9):2299-306
– reference: 15333590 - Hum Reprod Update. 2004 Nov-Dec;10(6):487-96
– reference: 20970977 - Curr Opin Cell Biol. 2011 Apr;23(2):150-6
– reference: 20036312 - Mol Cell Endocrinol. 2010 Jul 8;323(1):94-104
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Snippet Glucose-regulated protein 78 (GRP78) is highly expressed in first trimester cytrophoblastic cells (CTBs), especially in syncytiotrophoblast (STB). However, the...
Background Glucose-regulated protein 78 (GRP78) is highly expressed in first trimester cytrophoblastic cells (CTBs), especially in syncytiotrophoblast (STB)....
BACKGROUND: Glucose-regulated protein 78 (GRP78) is highly expressed in first trimester cytrophoblastic cells (CTBs), especially in syncytiotrophoblast (STB)....
Background Glucose-regulated protein 78 (GRP78) is highly expressed in first trimester cytrophoblastic cells (CTBs), especially in syncytiotrophoblast (STB)....
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StartPage e40596
SubjectTerms Achievement tests
Adult
Analysis
Antibodies
Apoptosis
Binding sites
Biology
Cancer
Cell culture
Cell Fusion
Cell Line, Tumor
Cell surface
Chemical inhibitors
Choriocarcinoma
Chorionic Gonadotropin - secretion
Colforsin - pharmacology
Deregulation
Down-Regulation - drug effects
Endoplasmic reticulum
Female
Forskolin
Fusion protein
Gene expression
Glucose
Gynecology
Heat-Shock Proteins - genetics
Heat-Shock Proteins - metabolism
Humans
Hypoxia
Medicine
Membrane fusion
Membranes
Morphology
mRNA
Obstetrics
Placenta
Plasma
Pre-eclampsia
Pre-Eclampsia - genetics
Pre-Eclampsia - metabolism
Pre-Eclampsia - pathology
Preeclampsia
Pregnancy
Pregnancy Trimester, First - genetics
Pregnancy Trimester, First - metabolism
Proteins
Relocation
RNA
Set-top boxes (Television)
siRNA
Trophoblasts - cytology
Trophoblasts - drug effects
Trophoblasts - metabolism
Trophoblasts - pathology
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Title Involvement of Membrane GRP78 in Trophoblastic Cell Fusion
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http://dx.doi.org/10.1371/journal.pone.0040596
Volume 7
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