Expression of Platelet Derived Growth Factor-A, C and Platelet Derived Growth Factor Receptor-alpha in the Ischemia Reperfusion Renal Failure Model / 대한신장학회잡지

BACKGOUND: Platelet-derived growth factor (PDGF) is a widely expressed growth factor with both mitogenic and chemotactic activities in many connective tissue cell types. There are four members of PDGF family; PDGF-A, PDGF-B, PDGF-C, PDGF-D. Their biological effects are mediated via two tyrosine kinase receptors, PDGF receptor-alpha and PDGF receptor-beta, and PDGF-mediated signaling is critical for development of many organ systems and acquired disease. The aims of this study were to determine the changes of PDGF-A, PDGF-C and PDGF receptor (PDGFR)-alpha expression in ischemia reperfusion acute renal failure model. METHODS: We examined the expression and localization of PDGF-A, PDGF-C and PDGF receptor-alpha protein using Western blot analysis and immunohistochemistry and PDGF-C mRNA using RNase protection assay after ischemia reperfusion renal failure model. RESULTS: PDGF-A expression showed no change after ischemia reperfusion injury. Proliferating cell nuclear antigen expression increased at day 2 after ischemia reperfusion injury. PDGF-C expression increased at day 2 after ischemia reperfusion injury, and was localized in tubular epithelial cells of outer medulla. PDGFR-alpha increased at day 2 after ischemia reperfusion injury, and was localized in tubular interstitium of outer medulla. CONCLUSION: These results indicated that PDGF-C and PDGF receptor-alpha may have an important role in the renal regeneration after ischemia reperfusion renal injury.

The Expressions of PDGF-C, PDGF-D and PDGF Receptors in Renal Development Model / 대한신장학회잡지

BACKGROUND: Four platelet derived growth factor (PDGF) family members have been identified; the classical PDGFs, PDGF-A and PDGF-B, and the novel PDGFs, PDGF-C and PDGF-D, which were only recently discovered. METHODS: The present study was designed to determine the changes of the platelet derived growth factor (PDGF) subtypes (C & D) and their receptors (PDGFR)-alpha & beta expression in kidneys during pre- and postnatal development. RESULTS: All the protein levels of PDGFR-alpha and -beta and the mRNA levels of PDGF-C and D were high in kidneys during the prenatal period and decreased differently during the postnatal period. PDGFR-alpha was expressed in the interstitial space at embryo day 18. PDGFR-beta protein were expressed in metanephric blastema at embryo day 18. PDGF-C mRNA was expressed in metanephric blastema, developing glomerulus at embryo 18 day and in collecting duct at postnatal day 7. PDGF-D mRNA was expressed in the parietal and vesceral epithelial cells during pre and postnatal period. CONCLUSION: These results indicate that the PDGF subtypes (C & D) and their receptors (PDGFR-alpha & -beta) are differently expressed in the kidney during the prenatal and postnatal period.

Apoptotic Effect of Radiocontrast Media on Human Umbilical Vein Endothelial Cells

The damage of vascular endothelial cells leads to the progression of vascular disease. Apoptotic damage of endothelial cells is an important mechanism in vascular disease. Recently, it has been reported that radiocontrast can induce vascular endothelial cell injury. The present study used terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and FACScan analysis to examine whether radiocontrast agenst, such as iopromide, sodium-meglumine-ioxithalamate or gadopentetate dimeglumine, induce apoptotic injury in human umbilical vein endothelial cells. In the study, iopromide, sodium-meglumine-ioxithalamate and gadopentetate dimeglumine brought about human umbilical vein endothelial cell death in phase-contrast microscopic findings. According to TUNEL and FACScan analysis, iopromide and sodium-meglumine- ioxithalamate induced apoptosis in vascular endothelial cells in a dose-dependent. The apoptotic effect of sodium-meglumine-ioxithalamate was shown to be greater than that of iopromide. Gadopentetate dimeglumine also induced apoptosis in human umbilical vein endothelial cells as observed by TUNEL and FACScan analysis. These results suggest that iopromide, which is a non-ionic radiocontrast agent, proved to be less apoptotic than sodium-meglumine-ioxithalamate. Gadopentetate dimeglumine, which is used MRI, has an apoptotic effect in vascular endothelial cells. Thus, apoptosis of endothelial cells by radiocontrast agents might induce deleterious effects on vascular endothelial integrity.

The Study on the Expression of Angiopoietin-1, Angiopoietin-2, and Tie2 in Mouse Kidney Maturation / 대한신장학회잡지

BACKGROUND: The Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2) and Tie2 have essential role in angiogenesis in development. Ang1 and Ang2 are ligands which binds to their receptor, Tie2. METHODS: Expression of these proteins was sought during mouse kidney maturation from embryonic day 16 (E16) to 28 days postnatal (P28). RESULTS: Using RNase protection assay and Western blot, these three molecules were expressed throughout the experimental period with peak levels at P28 (Ang1), P14 (Ang2) and P7 (Tie2). By immunohistochemical analysis, Ang1 protein was found to localize to condensing renal mesenchymal cells, and tubules. Ang2 proteins were detected in differentiating outer medullary tubules and the vasa recta bundle area. Tie2 protein was detected in a portion of glomerular tufts and cortical interstitium, and medulla including vessels in the vasa recta. CONCLUSIONS: These data suggest that Ang1, Ang2 and Tie2 proteins are expressed in renal development.

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

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.