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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2009-10-7
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pubmed:abstractText |
Lymphangioleiomyomatosis (LAM) is a potentially fatal lung disease characterized by nodules of proliferative smooth muscle-like cells. The exact nature of these LAM cells and their proliferative stimuli are poorly characterized. Herein we report the novel findings that the lymphangiogenic vascular endothelial growth factors (VEGF) C and D induce LAM cell proliferation through activation of their cognate receptor VEGF-R3 and activation of the signaling intermediates Akt/mTOR/S6. Furthermore, we identify expression of the proteoglycan NG2, a marker of immature smooth muscle cells, as a characteristic of LAM cells both in vitro and in human lung tissue. VEGF-C-induced LAM cell proliferation was in part a result of autocrine stimulation that resulted from cross talk with lymphatic endothelial cells. Ultimately, these findings identify the lymphangiogenic VEGF proteins as pathogenic growth factors in LAM disease and at the same time provide a novel pharmacotherapeutic target for a lung disease that to date has no known effective treatment.
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pubmed:commentsCorrections |
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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,
http://linkedlifedata.com/resource/pubmed/chemical/MTOR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteoglycans,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor C,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor D,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/chondroitin sulfate proteoglycan 4,
http://linkedlifedata.com/resource/pubmed/chemical/tuberous sclerosis complex 2 protein
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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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 |
1410-20
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19717640-Antigens,
pubmed-meshheading:19717640-Autocrine Communication,
pubmed-meshheading:19717640-Cell Proliferation,
pubmed-meshheading:19717640-Endothelial Cells,
pubmed-meshheading:19717640-Endothelium,
pubmed-meshheading:19717640-Enzyme Activation,
pubmed-meshheading:19717640-Humans,
pubmed-meshheading:19717640-Lymphangioleiomyomatosis,
pubmed-meshheading:19717640-Models, Biological,
pubmed-meshheading:19717640-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:19717640-Protein Kinases,
pubmed-meshheading:19717640-Proteoglycans,
pubmed-meshheading:19717640-Ribosomal Protein S6 Kinases,
pubmed-meshheading:19717640-Signal Transduction,
pubmed-meshheading:19717640-TOR Serine-Threonine Kinases,
pubmed-meshheading:19717640-Tumor Suppressor Proteins,
pubmed-meshheading:19717640-Vascular Endothelial Growth Factor C,
pubmed-meshheading:19717640-Vascular Endothelial Growth Factor D,
pubmed-meshheading:19717640-Vascular Endothelial Growth Factor Receptor-3
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pubmed:year |
2009
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pubmed:articleTitle |
Vascular endothelial growth factors C and D induces proliferation of lymphangioleiomyomatosis cells through autocrine crosstalk with endothelium.
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pubmed:affiliation |
Thoracic Disease Research Unit, Division of Pulmonary, Mayo Clinic, Rochester, MN 55905, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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