Renal ischemia reperfusion inhibits VEGF expression and induces ADAMTS-1, a novel VEGF inhibitor

David Basile, Katherine Fredrich, Bhadrani Chelladurai, Ellen C. Leonard, Alan R. Parrish

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume294
Issue number4
DOIs
StatePublished - Apr 2008

Fingerprint

Thrombospondin 1
Disintegrins
Metalloproteases
Vascular Endothelial Growth Factor A
Reperfusion
Ischemia
Reperfusion Injury
Kidney
Blood Vessels
Genes
CD13 Antigens
Messenger RNA
Wounds and Injuries
Microarray Analysis
Chronic Renal Insufficiency
Fluorescent Antibody Technique
Sprague Dawley Rats
Proteins
Western Blotting
Immunohistochemistry

Keywords

  • Microarray
  • Rarefaction

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Renal ischemia reperfusion inhibits VEGF expression and induces ADAMTS-1, a novel VEGF inhibitor. / Basile, David; Fredrich, Katherine; Chelladurai, Bhadrani; Leonard, Ellen C.; Parrish, Alan R.

In: American Journal of Physiology - Renal Physiology, Vol. 294, No. 4, 04.2008.

Research output: Contribution to journalArticle

Basile, David ; Fredrich, Katherine ; Chelladurai, Bhadrani ; Leonard, Ellen C. ; Parrish, Alan R. / Renal ischemia reperfusion inhibits VEGF expression and induces ADAMTS-1, a novel VEGF inhibitor. In: American Journal of Physiology - Renal Physiology. 2008 ; Vol. 294, No. 4.
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