Gene expression of VEGF and its receptors Flk-1/KDR and Flt-1 in cultured and transplanted rat islets
| Autor: | B, Vasir, J C, Jonas, G M, Steil, J, Hollister-Lock, W, Hasenkamp, A, Sharma, S, Bonner-Weir, G C, Weir |
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| Rok vydání: | 2001 |
| Předmět: |
Blood Glucose
Male Vascular Endothelial Growth Factor A Islets of Langerhans Transplantation Gene Expression Endothelial Growth Factors Diabetes Mellitus Experimental Rats Sprague-Dawley Mice Organ Culture Techniques Antigens CD Reference Values Animals Receptors Growth Factor Postoperative Period RNA Messenger Extracellular Matrix Proteins Lymphokines Nonmuscle Myosin Type IIB Vascular Endothelial Growth Factor Receptor-1 Myosin Heavy Chains Vascular Endothelial Growth Factors Myocardium Nuclear Proteins Receptor Protein-Tyrosine Kinases Cadherins Hypoxia-Inducible Factor 1 alpha Subunit Hormones Rats DNA-Binding Proteins Mice Inbred C57BL Receptors Vascular Endothelial Growth Factor Rats Inbred Lew Hypoxia-Inducible Factor 1 Transcription Factors |
| Zdroj: | Transplantation. 71(7) |
| ISSN: | 0041-1337 |
| Popis: | Vascular endothelial growth factor (VEGF) and its two receptor tyrosine kinases, Flk-1/KDR and Flt-1, may play an important role in mediating the revascularization of transplanted pancreatic islets.Using semiquantitative multiplex reverse-transcribed polymerase chain reaction we determined the gene expression of VEGF and its receptors in cultured and transplanted rat islets.After exposure of islet cells to hypoxia in vitro, increases were found in the gene expression of the VEGF120 and VEGF164 isoforms, with simultaneous increases in VE-cadherin, Flk-1/KDR, and Flt-1. In vivo studies consisted of analysis of islet grafts transplanted into both normal and diabetic recipients. Expression of both VEGF120 and VEGF164 in grafts was up-regulated for the first 2-3 days after transplantation, with the response being more prolonged in the diabetic rats. These increases were followed by reduced expression of VEGF on days 5, 7, and 9. Increases in the expression of VE-cadherin in islet grafts in normal and diabetic recipients tended to parallel VEGF expression, with the increases in both probably being caused by hypoxia. The early increases of VEGF expression were followed by a rise in the expression of VEGF receptors, which probably represents the early stages of angiogenesis. Graft expression of Flk-1/KDR and Flt-1 was enhanced at 3 and 5 days in the normoglycemic recipients, while in the diabetic recipients increases were found later on days 5, 7, and 14.The delayed expression of VEGF receptors in the diabetic recipients could reflect impaired angiogenesis caused by the diabetic milieu; this delay could contribute to the less outcomes of grafts transplanted into a hyperglycemic environment. |
| Databáze: | OpenAIRE |
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