Stability and Species Specificity of Renal VEGF-A Splicing Patterns in Kidney Disease.
Vascular endothelial growth factor A (VEGF-A) is essential for maintaining the glomerular filtration barrier. Absolute renal levels of VEGF-A change in patients with diabetic nephropathy and inflammatory kidney diseases, but whether changes in the renal splicing patterns of VEGF-A play a role remains unclear. In this study, we investigated mRNA splicing patterns of pro-angiogenic isoforms of VEGF-A in glomeruli and whole kidney samples from human patients with kidney disease and from mouse models of kidney disease. Kidney biopsies were obtained from patients with acute rejection following kidney transplantation, patients with diabetic nephropathy, and control subjects. In addition, kidney samples were obtained from mice with lupus nephritis, mice with diabetes mellitus, and control mice. The relative expression of each VEGF-A splice variant was measured using RT-PCR followed by quantitative fragment analysis. The pattern of renal VEGF-A splice variants was unchanged in diabetic nephropathy and lupus nephritis and was stable throughout disease progression in acute transplant rejection and diabetic nephropathy; these results suggest renal VEGF-A splicing stability during kidney disease. The splicing patterns were species-specific; in the control human kidney samples, VEGF-A 121 was the dominant isoform, whereas VEGF-A 164 was the dominant isoform measured in the mouse kidney samples.
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
R J
RJ
Turner
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
M
M
Eikmans
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
I M
IM
Bajema
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
J A
JA
Bruijn
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
H J
HJ
Baelde
D017398:Alternative Splicing; D000818:Animals; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation; D008181:Lupus Nephritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D013045:Species Specificity; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse