Erythropoietin (EPO) Protects Against Angiotensin II-Induced Apoptosis and Promotes Angiogenesis of Glomerular Endothelial Cells
HC Yang, YQ Zuo, LJ Ma, AB Fogo. Vanderbilt University, Nashville, TN
Background: EPO promotes cell survival by binding its receptor, EPO-R, and activating JAK-2 and down-stream signaling cascades in endothelial cells. The aim of the present study was to investigate whether EPO could specifically protect glomerular endothelial cells (GEN) against injury and the possible mechanisms.
Design: Glomerular endothelial cell line was derived from SV40 mice (gift from Dr. Madaio), and divided into four groups: GEN, without any treatment; EPO, treated with 10-4 M mouse recombinant EPO; Ang II, treated with 10-7 M angiotensin II; Ang II+EPO, treated with both EPO and Ang II. Cells were harvested at 48h.
Results: EPO protected GEN against Ang II-induced apoptosis (Ang II 13.40.1% vs. Ang II+EPO 6.250.15%, P<0.05). This effect of EPO was paralleled by a decrease in caspase 3 activation (Ang II 1.270.02 vs. Ang II+EPO 0.890.16, P<0.05). We also found that Ang II decreased GEN migration (GEN 27.94.2% vs. Ang II 22.71.6, P<0.05), and EPO restored GEN migration (Ang II+EPO 26.91.12%, P<0.05). EPO also preserved VEGF receptor 2 (Flk-1) phosphorylation (Ang II 0.190.02 vs. Ang II+EPO 0.690.14, P<0.05), but there was no effect on endothelial nitric oxide synthase (eNOS) expression (Ang II 0.0930.01 vs. Ang II+EPO 0.0590.02, pNS). Akt is pivotal in angiogenesis and in promoting cell survival. In our study, Akt phosphorylation was improved by EPO in GEN injured by Ang II (Ang II 0.6450.01 vs. Ang II+EPO 0.8840.10, P<0.05).
Conclusions: Our data suggest that EPO has direct effects on GEN to promote angiogenesis and protect against Ang II-induced apoptosis, possibly related to Akt phosphorylation and synergistic interactions with VEGF.
Category: Kidney (does not include tumors)
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 189, Tuesday Afternoon