The Antiapoptotic Effect of Vascular Endothelial Growth Factor and Angiopoietin-1 on Glomerular Endothelial Cells in Adriamycin or Cisplatin-induced Apoptosis / 대한신장학회잡지

ABSTRACT

BACKGROUND: Because glomerular endothelium play a pivotal role in the renal diseases, damage of glomerular endothelial cells lead to progression of glomerular sclerosis and decrement of renal function. Apoptotic damage of cells is an important mechanism in renal disease. Therefore, several growth factors that have antiapoptotic effect may have a protective role in maintaining a renal function in apoptotic cell injury. METHODS: The present study evaluated whether cisplatin or adriamycin induce apoptosis in glomerular endothelial cells. We also evaluated the antiapoptotic effect of angiopoietin-1 and VEGF in cisplatin or adriamycin- induced apoptosis. RESULTS: Cisplatin or adriamycin induced apoptosis in glomerualr endothelial cell in dose dependent manner. Angiopoietin-1 and VEGF produced antiapoptotic effect in cisplatin or adriamycin-induced apoptosis in a dose dependent manner. The antiapoptotic effect of angiopoietin-1 was more potent than that of VEGF in glomerualr endothelial cells. Wortmannin, a phosphatidylinositol 3'-kinase inhibitor decrease the angiopoietin-1 or VEGF-induced antiapoptotic effect. CONCLUSION: These results suggest that angiopoietin-1 and VEGF may be a strong survival factor for the glomerular endothelial cells in the cisplatin or adriamycin-induced apoptosis through phosphatidylinositol 3'-kinase/Akt. Therefore, pretreatment of angiopoietin-1 and VEGF could play a beneficial role for maintaining normal glomerular endothelial cell integrity before and during systemic cisplatin or adriamycin therapy.