Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells

Abstract

Vascular endothelial growth factor (VEGF) acts primarily as an endothelial cell mitogen via the "endothelial cell-specific" receptors VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR). Only a few nonendothelial cells have been shown to possess functional VEGF receptors. We therefore examined the rat renal tubular epithelial cell line NRK52-E. NRK52-E expressed VEGFR-1 and VEGFR-2 mRNA and protein by RT-PCR, Northern blotting, Western blotting, immunofluorescence, and ligand binding. Serum-starved NRK52-E incubated with VEGF showed a significant increase in [(3)H]thymidine incorporation compared with control (2.3-fold at 1-10 ng/ml, P < 0. 05; 3.3-fold at 50-100 ng/ml, P < 0.01). VEGF also protected NRK52-E from hydrogen peroxide-induced apoptosis and necrosis compared with control (annexin-V-FITC-positive cells, 39 vs. 54%; viable cells, 50. 5 vs. 39.7%). Immunohistochemical staining using a variety of antibodies showed expression of both VEGF receptors in normal rat renal tubules in vivo. Because VEGF induced a proliferative and an antiapoptotic response in renal tubular epithelial cells, these data suggest that VEGF may act as a survival factor for renal tubular epithelium in vivo.

Enhancement of in vitro human tubulogenesis by endothelial cell-derived factors: implications for in vivo tubular regeneration after injury

“…VEGF induces a proliferative and an antiapoptotic response in tubular cells and acts as a survival factor for these cells (11,34). The expression of VEGF by endothelial cells is stimulated in response to hypoxia to preserve the capillary blood supply (14) and to promote tubular cell survival and recovery (28).…”

Inhibition of tubulointerstitial fibrosis by pentoxifylline is associated with improvement of vascular endothelial growth factor expression

“…VEGF is a survival factor for vascular endothelial cells and plays an important role in the homeostasis of vascular endothelium [2,9] . VEGF is also a survival factor for renal tubular epithelial cells and is involved in renal tubule construction [13][14][15] . Supplemention with VEGF improved the interstitial injury mediated by cyclosporine [29] .…”

“…Furthermore, VEGF has been shown to induce nephrogenesis and vasculogenesis in all renal tubular epithelial cells [13,14] . VEGF induced a proliferative response while preventing hydrogen peroxideinduced apoptosis and necrosis in renal tubular epithelial cells [15] . This suggests that VEGF may act as a survival factor for the tubular epithelium.…”

Potential Interventions in Sepsis-Related Acute Kidney Injury

“…These compounds include growth factors and antiapoptotic substances. Numerous growth factors, including IGF, hepatocyte growth factor, and vascular endothelial growth factor, have important antiapoptotic and pro-proliferation effects, with promising results in animal studies (137)(138)(139)(140). Unfortunately, early clinical trials have not yielded consistent results (141,142) and further studies are under way.…”