Renal ischemia reperfusion inhibits VEGF expression and induces ADAMTS-1, a novel VEGF inhibitor
| Autor: | Bhadrani Chelladurai, Ellen C. Leonard, Alan R. Parrish, Katherine Fredrich, David P. Basile |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A medicine.medical_specialty Pathology Physiology Renal Circulation Rats Sprague-Dawley Renal Artery ADAMTS1 Protein Internal medicine Gene expression medicine Animals RNA Messenger Receptor DNA Primers Oligonucleotide Array Sequence Analysis Regulation of gene expression Kidney Renal circulation Renal ischemia Reverse Transcriptase Polymerase Chain Reaction Microarray analysis techniques business.industry ADAMTS Rats ADAM Proteins Receptors Vascular Endothelial Growth Factor medicine.anatomical_structure Endocrinology Gene Expression Regulation Reperfusion Injury business |
| Zdroj: | American Journal of Physiology-Renal Physiology. 294:F928-F936 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00596.2007 |
| Popis: | Reductions in vascular density occur following acute ischemia-reperfusion (I/R) injury that may predispose the development of chronic kidney disease. The mechanisms mediating vascular loss are not clear but may relate to the lack of effective vascular repair responses. To determine the regulation of the VEGF/VEGFR pathway following I/R injury, male Sprague-Dawley rats were subjected to bilateral renal ischemia (45 min) and allowed to recover for 1, 3, 7, and 35 days. VEGF mRNA expression was repressed by greater than 50% of control values up to 3 days postischemia, while VEGF protein was repressed for up to 7 days postischemia. The renal mRNA expression of receptors was not altered postischemia; however, VEGFR1 (flt-1) protein was transiently reduced in kidney while soluble flt-1 was elevated in plasma at 7 days following injury. Microarray analysis of angiogenesis-related genes identified the enhanced expression of a number of genes, among these was ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin motif-1), a secreted VEGF inhibitor. The altered expression of ADAMTS-1 was confirmed using RT-PCR and Western blot analysis; immunofluorescence localized its expression to proximal tubules following I/R injury. Other genes identified using microarray included aminopeptidase N, Smad-1, and Id-3 and their localization was also examined using immunohistochemistry. In summary, the data indicate no clear pattern of anti-angiogenic gene expression following renal I/R injury. However, the studies do suggest an overall inhibition of the VEGF pathway during the early injury and repair phase of renal ischemia that may contribute to an overall reduction in renal microvascular density. |
| Databáze: | OpenAIRE |
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