| Effects of thrombin on RPE cells are mediated by transactivation of growth factor receptors. | |
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MedLine Citation:
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PMID: 19369239 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To determine the expression of blood coagulation factors and thrombin receptors in retinal pigment epithelial (RPE) cells and whether the effects of thrombin on the chemotaxis and the secretion of VEGF are mediated by transactivation of growth factor receptors. METHODS: Gene expression in acutely isolated and cultured human RPE cells was evaluated by RT-PCR. Alterations in gene expression and secretion of VEGF were determined by real-time RT-PCR and ELISA, respectively. Chemotaxis was examined with a Boyden chamber assay. RESULTS: RPE cells expressed the mRNA of the protease-activated receptors PAR1 and -3 and of various coagulation factors (III, V, VII, VIII, and X). Thrombin stimulated the expression and secretion of VEGF-A from RPE cells, decreased the expression of VEGFD, and increased the gene expression of VEGFR-1 (FLT1). The effects on the secretion of VEGF-A and the increase in FLT1 expression were mediated by stimulation of the secretion of TGF-beta1 and activation of the TGF-beta activin receptor-like kinase. Thrombin stimulated the chemotaxis of RPE cells, and this effect was mediated by transactivation of the PDGF receptor tyrosine kinase. CONCLUSIONS: The expression of different coagulation factors suggests that RPE cells provide a procoagulant surface for the formation of thrombin from prothrombin via the extrinsic coagulation pathway. Thrombin stimulates the secretion of VEGF-A, the expression of FLT1, and the chemotaxis of RPE cells via transactivation of TGF-beta and PDGF receptors, respectively. |
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Authors:
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Margrit Hollborn; Carola Petto; Anja Steffen; Susanne Trettner; Andrea Bendig; Peter Wiedemann; Andreas Bringmann; Leon Kohen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-04-15 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 50 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-08-28 Completed Date: 2009-09-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 4452-9 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology and Eye Hospital, Center of Clinical Research (IZKF), University of Leipzig, Leipzig, Germany. hollbm@medizin.uni-leipzig.de |
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| MeSH Terms | |
Descriptor/Qualifier:
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Blood Coagulation Factors
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genetics,
metabolism Blotting, Western Cells, Cultured Chemotaxis / drug effects Enzyme-Linked Immunosorbent Assay Humans RNA, Messenger / metabolism Receptors, Platelet-Derived Growth Factor / genetics*, metabolism Receptors, Thrombin / genetics, metabolism Receptors, Transforming Growth Factor beta / genetics*, metabolism Retinal Pigment Epithelium / drug effects*, metabolism Reverse Transcriptase Polymerase Chain Reaction Thrombin / pharmacology* Transcriptional Activation* Vascular Endothelial Growth Factor A / genetics, metabolism Vascular Endothelial Growth Factor Receptor-1 / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Blood Coagulation Factors; 0/RNA, Messenger; 0/Receptors, Thrombin; 0/Receptors, Transforming Growth Factor beta; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; EC 2.7.1.112/Receptors, Platelet-Derived Growth Factor; EC 2.7.1.112/Vascular Endothelial Growth Factor Receptor-1; EC 2.7.10.1/FLT1 protein, human; EC 3.4.21.5/Thrombin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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