Received February 26, 2004
Revised March 24, 2004
Accepted after revision April 26, 2004
Divergence of renal VEGF mRNA expression and protein level in postischemic rat kidneys
Adam Vannay 1*,
Andrea Fekete 2,
Csaba Adori 3,
Tibor Toth 2,
György Losonczy 2,
Lajos Laszlo 4,
Barna Vasarhelyi 5,
Tivadar Tulassay 1,
Andras Szabo 2
1 Semmelweis University-Hungarian Academy of Sciences
2 Semmelweis University
3 Eötvös University of Sciences
4 Eötös University of Sciences
5 Hungarian Academy of Sciences
* To whom correspondence should be addressed. E-mail: vannay{at}gyer1.sote.hu.
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Abstract |
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Vascular endothelial growth factor (VEGF) is a potent factor of angiogenesis and vascular protection. VEGF synthesis is induced by hypoxia and different cytokines including interleukin-6 (IL-6) and interleukin-1 
(IL-1). Postischemic alterations of this growth factor, however, in the kidney are incompletely known. To determine VEGF synthesis in renal ischemia/reperfusion (I/R) injury unilateral warm ischemia was induced by cross-clamping the left renal pedicle for 55 minutes followed by 2 and 24 hours of reperfusion (T2 and T24 kidneys; n=6/group). Sham-operated, non-clamped animals served as controls (n=6/group). Renal VEGF, IL-6 and IL-1 mRNA expression were determined by reverse transcription-polymerase chain reaction (RT-PCR). VEGF protein level and distribution were determined by Western blot and immunohistochemical analysis.
Immunohistochemistry revealed prominent VEGF staining in the outer medulla of control, T2 and T24 kidneys. VEGF immunoreactivity accumulated at the basolateral area of tubular epithelial cells in T2 kidneys, while it was diffuse in control and T24 kidneys. VEGF protein levels were 2-3-fold increased in T2 and T24 kidneys (both P <0.01 vs. controls), while VEGF mRNA expression remained unchanged. IL-6 mRNA expression was increased (P <0.01 vs. controls) in T2 kidneys, while IL-1 mRNA expression remained unchanged.
Increased VEGF protein levels but not mRNA expression suggests that during renal I/R injury VEGF synthesis - distinct from other organs - is primarily regulated at a post-transcriptional level. Since IL-6 mRNA expression increased simultaneously with VEGF protein levels, the postischemic regulation of IL-6 and VEGF synthesis might be interrelated in rat kidney.
Key Words:
Gene expression, Ischaemia, Kidney
