| IGF2 actions on trophoblast in human placenta are regulated by the insulin-like growth factor 2 receptor, which can function as both a signaling and clearance receptor. | |
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MedLine Citation:
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PMID: 20980691 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Insulin-like growth factor 2 (IGF2) enhances proliferation and survival of human first-trimester cytotrophoblasts (CTB) by signaling through the insulin-like growth factor 1 receptor (IGF1R). However, the role of the IGF2 receptor (IGF2R) in regulating trophoblast kinetics is unclear: It could act as a clearance receptor for trafficking excess ligand to lysosomes for degradation and/or directly mediate IGF2 signaling. We used an IGF2R knockdown strategy in BeWo cells and placental villous explants to investigate trophoblast proliferation and survival in response to stimulation by IGF. Both IGF1 and IGF2 significantly (P < 0.001) increased mitosis and reduced apoptosis in serum-starved BeWo cells. Small interfering RNA (siRNA)-mediated knockdown of IGF2R further enhanced IGF2-stimulated mitosis (P < 0.01), and IGF2-mediated rescue of apoptosis (P < 0.001) in these cells. Leu(27)IGF2, an IGF2 analogue that binds to IGF2R but not IGF1R, also protected IGF2R-expressing BeWo cells from apoptosis but did not increase mitosis. IGF treatment of term placental villous explants with reduced syncytial expression of IGF2R increased CTB proliferation (P < 0.001) and decreased apoptosis (P < 0.01) compared to untreated controls. Moreover, IGF2-mediated rescue of CTB apoptosis was significantly greater than that in tissue with normal IGF2R expression. Leu(27)IGF2 promoted mitogenesis and survival only in explants with intact IGF2R expression. Given that altered CTB turnover is observed in pregnancies complicated by fetal growth restriction, the development of strategies to manipulate the IGF2R signaling axis in the syncytiotrophoblast may provide a therapeutic avenue for treating this condition. |
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Authors:
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Lynda K Harris; Ian P Crocker; Philip N Baker; John D Aplin; Melissa Westwood |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-27 |
Journal Detail:
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Title: Biology of reproduction Volume: 84 ISSN: 1529-7268 ISO Abbreviation: Biol. Reprod. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-23 Completed Date: 2011-06-14 Revised Date: 2012-03-01 |
Medline Journal Info:
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Nlm Unique ID: 0207224 Medline TA: Biol Reprod Country: United States |
Other Details:
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Languages: eng Pagination: 440-6 Citation Subset: IM |
Affiliation:
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Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Sciences Centre, St. Mary’s Hospital, Oxford Road, Manchester, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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metabolism,
physiology Cell Survival / drug effects, genetics Cells, Cultured Female Gene Knockdown Techniques Humans Insulin-Like Growth Factor II / metabolism, pharmacokinetics*, pharmacology*, physiology Metabolic Clearance Rate Mitosis / drug effects, genetics Models, Biological Placenta / drug effects*, metabolism, physiology Pregnancy Protein Processing, Post-Translational / physiology RNA, Small Interfering / pharmacology Receptor, IGF Type 2 / antagonists & inhibitors, genetics, metabolism, physiology* Transfection Trophoblasts / cytology, drug effects*, metabolism, physiology |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/RNA, Small Interfering; 0/Receptor, IGF Type 2; 67763-97-7/Insulin-Like Growth Factor II |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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