Quantitave and qualitative changes in vascular endothelial growth factor gene expression in glomeruli of patients with type 2 diabetes.
OBJECTIVE
Vascular endothelial growth factor (VEGF) exists in three main splice variants, characterized by 121, 165 and 189 amino acids (VEGF 121, VEGF 165 and VEGF 189) and acts via two specific receptors: VEGF-R1 or Flt-1 and VEGF-R2 or KDR. VEGF plays an important role in the pathogenesis of diabetic retinopathy. This study examined the relationship between VEGF and its isoforms and the severity of diabetic nephropathy in type 2 diabetes.


METHODS
We evaluated the glomerular gene expression of VEGF and its receptors and studied the relationships with renal functional and structural parameters in type 2 diabetic patients.


METHODS
Glomeruli from 17 kidney biopsies were microdissected; 14 out of 17 biopsies were also subjected to electron microscopic morphometric analysis to estimate glomerular structural parameters. VEGF mRNA was studied by comparative kinetic RT-PCR and real-time RT-PCR in order to identify the three different isoforms and to quantify VEGF, VEGF-R1 and VEGF-R2 mRNA levels.


RESULTS
(i) Glomerular VEGF mRNA levels were inversely related to albumin excretion rate (r=-0.66, P=0.004); (ii) both the degree of mesangial and mesangial matrix expansion were inversely related to VEGF 165 mRNA levels (r=-0.73, P=0.005 and r=-0.64, P=0.017), and directly to VEGF 121 mRNA levels (r=0.74, P=0.003 and r=0.73, P=0.004); and (iii) VEGF and VEGF-R2 mRNA levels were directly related (r=0.62, P=0.033).


CONCLUSIONS
These findings suggested that quantitative and qualitative changes in VEGF expression are present in type 2 diabetic patients with nephropathy and might be involved in the pathogenesis and progression of diabetic glomerulopathy.
Bortoloso
Elena
E
Department of Medical and Surgical Sciences, Division of Nephrology, Laboratory of Molecular Biology, University of Padua, Padua, Italy.
Del Prete
Dorella
D
Dalla Vestra
Michele
M
Gambaro
Giovanni
G
Saller
Alois
A
Antonucci
Francesco
F
Baggio
Bruno
B
Anglani
Franca
F
Fioretto
Paola
P
D000368:Aged; D000419:Albuminuria; D017398:Alternative Splicing; D001706:Biopsy; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor