Vascular endothelial growth factor (VEGF) and soluble VEGF receptor FLT-1 in diabetic nephropathy

Nan Hee Kim, Jeong Heon Oh, Ji A. Seo, Kye Won Lee, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Young Sun Kang, Sang Youb Han, Kum Hyun Han, Yi Hwa Ji, Dae Ryong Cha

Research output: Contribution to journalArticle

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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. Conclusion. 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.

Original languageEnglish
Pages (from-to)167-177
Number of pages11
JournalKidney International
Volume67
Issue number1
DOIs
Publication statusPublished - 2005 Jan 1

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Vascular Endothelial Growth Factor Receptor-1
Diabetic Nephropathies
Vascular Endothelial Growth Factor A
Albumins
Creatinine
Angiotensin II
Glucose
Vascular Endothelial Growth Factor Receptor
Losartan
Reverse Transcription
Healthy Volunteers
Enzyme-Linked Immunosorbent Assay

Keywords

  • Albuminuria
  • DM nephropathy
  • Proximal tubule cell
  • SFLT-1
  • VEGF

ASJC Scopus subject areas

  • Nephrology

Cite this

Vascular endothelial growth factor (VEGF) and soluble VEGF receptor FLT-1 in diabetic nephropathy. / Kim, Nan Hee; Oh, Jeong Heon; Seo, Ji A.; Lee, Kye Won; Kim, Sin Gon; Choi, Kyung Mook; Baik, Sei Hyun; Choi, Dong Seop; Kang, Young Sun; Han, Sang Youb; Han, Kum Hyun; Ji, Yi Hwa; Cha, Dae Ryong.

In: Kidney International, Vol. 67, No. 1, 01.01.2005, p. 167-177.

Research output: Contribution to journalArticle

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AU - Kim, Nan Hee

AU - Oh, Jeong Heon

AU - Seo, Ji A.

AU - Lee, Kye Won

AU - Kim, Sin Gon

AU - Choi, Kyung Mook

AU - Baik, Sei Hyun

AU - Choi, Dong Seop

AU - Kang, Young Sun

AU - Han, Sang Youb

AU - Han, Kum Hyun

AU - Ji, Yi Hwa

AU - Cha, Dae Ryong

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AB - 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. Conclusion. 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.

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