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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2009-7-27
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pubmed:abstractText |
Glypicans are heparan sulfate proteoglycans that are bound to the cell surface by glycosylphosphatidylinositol. While six members of the glypican family are known in mammals, our study focused on glypican 3 (GPC3). Loss-of-function mutations of GPC3 result in the Simpson-Golabi-Behmel syndrome, an X-linked disorder characterized by pre- and postnatal liver and other organ overgrowth. GPC3 is overexpressed in human hepatocellular carcinoma; however, its role in normal liver regeneration and hepatocyte proliferation is unknown. Here we investigated the role of GPC3 in hepatocyte proliferation. GPC3 mRNA and protein levels begin to increase 2 days after hepatectomy with peak expression levels by day 5. In hepatocyte cultures, GPC3 reaches a plateau when hepatocyte proliferation decreases. In vitro studies using Morpholino oligonucleotides showed that blocking GPC3 expression promoted hepatocyte growth. Yeast two-hybrid assays revealed that GPC3 interacts with CD81, a member of the tetraspanin family that is reported to be involved in hepatitis C virus infection and cell proliferation. We found that CD81 levels also increased 2 days after partial hepatectomy and toward the end of regeneration. Immunofluorescence showed that CD81 and GPC3 colocalize by 2 and 6 days after hepatectomy. Co-immunoprecipitation validated the interaction of GPC3 and CD81. Our results indicate that GPC3 may be a negative regulator of liver regeneration and hepatocyte proliferation, and that this regulation may involve CD81.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-10231373,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-10402475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-10463591,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-10480909,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-11106655,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-11292377,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-12417406,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-12478660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-12479862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-12576633,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-12970454,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-15475451,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-15611341,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-15887976,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-15920546,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-16024626,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-16394126,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-1695320,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-17006932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-17117158,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-17559071,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-177845,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-18785116,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-18787398,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-8601590,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-8958336,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-9082986,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-9597125,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-9802880,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-9853964,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574424-9862855
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD81,
http://linkedlifedata.com/resource/pubmed/chemical/CD81 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cd81 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Glypicans,
http://linkedlifedata.com/resource/pubmed/chemical/Gpc3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1525-2191
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
175
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
717-24
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19574424-Animals,
pubmed-meshheading:19574424-Antigens, CD81,
pubmed-meshheading:19574424-Cell Proliferation,
pubmed-meshheading:19574424-Gene Knockdown Techniques,
pubmed-meshheading:19574424-Glypicans,
pubmed-meshheading:19574424-Hepatocytes,
pubmed-meshheading:19574424-Humans,
pubmed-meshheading:19574424-Immunoprecipitation,
pubmed-meshheading:19574424-Liver Regeneration,
pubmed-meshheading:19574424-Male,
pubmed-meshheading:19574424-Membrane Proteins,
pubmed-meshheading:19574424-Neuropeptides,
pubmed-meshheading:19574424-RNA, Messenger,
pubmed-meshheading:19574424-Rats,
pubmed-meshheading:19574424-Rats, Inbred F344,
pubmed-meshheading:19574424-Two-Hybrid System Techniques
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pubmed:year |
2009
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pubmed:articleTitle |
Investigation of the role of glypican 3 in liver regeneration and hepatocyte proliferation.
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pubmed:affiliation |
Department of Pathology, University of Pittsburgh School of Medicine, S-410 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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