Divergence of renal vascular endothelial growth factor mRNA expression and protein level in post‐ischaemic rat kidneys

Abstract

Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and vascular protection. Synthesis of VEGF is induced by hypoxia and different cytokines including interleukin-6 (IL-6) and interleukin-1β (IL-1β). However, post-ischaemic alterations of this growth factor in the kidney are incompletely known. To determine VEGF synthesis in renal ischaemia/reperfusion (I/R) injury unilateral warm ischaemia was induced by cross-clamping the left renal pedicle for 55 min followed by 2 and 24 h of reperfusion (T 2 and T 24 kidneys; n = 6 in each group). Sham-operated, non-clamped animals served as controls (n = 6). Renal VEGF, IL-6 and IL-1β 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, T 2 and T 24 kidneys. VEGF immunoreactivity accumulated at the basolateral area of tubular epithelial cells in T 2 kidneys, while it was diffuse in control and T 24 kidneys. VEGF protein levels were increased 2-to 3-fold in T 2 and T 24 kidneys (both P < 0.01 versus controls), while VEGF mRNA expression remained unchanged. IL-6 mRNA expression was increased (P < 0.01 versus controls) in T 2 kidneys, while IL-1β mRNA expression remained unchanged. Increased VEGF protein levels but not mRNA expression suggests that during renal I/R injury VEGF synthesis in kidneys -unlike in other organs -is primarily regulated at a post-transcriptional level. As IL-6 mRNA expression increased simultaneously with VEGF protein levels, the post-ischaemic regulation of IL-6 and VEGF synthesis might be interrelated in rat kidney.

Renal Cyst Development in Mice with Conditional Inactivation of the von Hippel-Lindau Tumor Suppressor

“…We observed that, in addition to normal VEGF expression in the outer medulla (48), four of nine cysts in one of the three mice examined expressed VEGF (Fig. 6F).…”

Simultaneous monitoring of multiple urinary cytokines may predict renal and patient outcome in ischemic AKI

“…VEGF is a growth factor that specifically promotes endothelial cell proliferation, differentiation, and survival, as well as mediating endothelium-dependent vasodilatation, inducing microvascular hyperpermeability, and participating in interstitial matrix remodeling. 38 Although VEGF protein levels have been reported to increase in postischemic rat kidneys, 39 the role of VEGF in human renal pathophysiology has not been clarified. [38][39][40] The possible role of EGF in renal growth or maturation and decreased urinary EGF excretion in children with AKI has been reported.…”

“…38 Although VEGF protein levels have been reported to increase in postischemic rat kidneys, 39 the role of VEGF in human renal pathophysiology has not been clarified. [38][39][40] The possible role of EGF in renal growth or maturation and decreased urinary EGF excretion in children with AKI has been reported. 41 Our findings suggest that TGF-a and VEGF may be involved in inflammatory processes and that EGF is involved in regenerative processes in human ischemic AKI.…”

Vascular Endothelial Growth Factor Protein Expression in a Renal Ablation Rabbit Model under Prolonged Warm and Cold Ischemia

“…We favor the investigation of VEGF protein instead of VEGFmRNA, based on a previous observation that VEGF synthesis during ischemia/reperfusion injury is regulated, in the postischemic kidney, at a post-transcriptional rather than at a transcriptional level [14]. The regulation of the two VEGF receptors is equally interesting, as hitherto previously investigated [15].…”