title: Vascular endothelial growth factor (VEGF) and soluble VEGF receptor FLT-1 in diabetic nephropathy.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) and its receptors have been implicated in the pathogenesis of diabetic nephropathy. The objective of this study was to determine whether alterations of the plasma and urinary VEGF and sFLT-1 levels were related to the stages and risk factors of diabetic nephropathy. In addition, we also examined the regulation of the VEGF/sFLT-1 expression by various stimuli in cultured human proximal tubule cells (HPTC).
  
  
  METHODS
  A total of 107 type 2 diabetic patients and 47 healthy control subjects were studied. The expression and protein levels of VEGF and sFLT-1 were measured by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  The urinary VEGF and sFLT-1 excretions were significantly increased in the microalbuminuric and proteinuric diabetic patients. The urinary VEGF levels were positively correlated with the urinary albumin to creatinine ratio (ACR), urinary sFLT-1 levels, and negatively correlated with creatinine clearance. The urinary sFLT-1 levels also showed a positive relationship with the urinary ACR. In cultured HPTC, high glucose stimuli rapidly up-regulated VEGF synthesis without having any effect on sFLT-1 synthesis. Interestingly, angiotensin II (Ang II) induced a dose-dependent increase in the synthesis of both VEGF and sFLT-1, which was significantly blocked by losartan.
  
  
  CONCLUSIONS
  The urinary excretion of VEGF and sFLT-1 increased at a relatively early stage in diabetic nephropathy associated with urinary albumin excretion. A marked increase in both VEGF/sFLT-1 synthesis in response to Ang II was observed in HPTC, which was different from the response to glucose stimuli. These findings may imply that VEGF and sFLT-1 can actively take part in the pathogenesis of diabetic nephropathy.
authors.affiliation: Department of Internal Medicine, Korea University, Ansan City, Kyungki-Do, Republic of Korea.
authors.forename: Nan Hee
authors.initials: NH
authors.lastname: Kim
authors.forename: Jeong Heon
authors.initials: JH
authors.lastname: Oh
authors.forename: Ji A
authors.initials: JA
authors.lastname: Seo
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Sin Gon
authors.initials: SG
authors.lastname: Kim
authors.forename: Kyung Mook
authors.initials: KM
authors.lastname: Choi
authors.forename: Sei Hyun
authors.initials: SH
authors.lastname: Baik
authors.forename: Dong Seop
authors.initials: DS
authors.lastname: Choi
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Kang
authors.forename: Sang Youb
authors.initials: SY
authors.lastname: Han
authors.forename: Kum Hyun
authors.initials: KH
authors.lastname: Han
authors.forename: Yi Hwa
authors.initials: YH
authors.lastname: Ji
authors.forename: Dae Ryong
authors.initials: DR
authors.lastname: Cha
mesh_terms: D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology; D001483:Base Sequence; D016022:Case-Control Studies; D002460:Cell Line; D004247:DNA / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics* / Q000378:metabolism* / Q000652:urine; D040281:Vascular Endothelial Growth Factor Receptor-1
chemical_list: D011506:Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D004247:DNA; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D005947:Glucose