Albumin suppresses vascular endothelial growth factor via alteration of hypoxia-inducible factor/hypoxia-responsive element pathway

Pisut Katavetin, Reiko Inagi, Toshio Miyata, Tetsuhiro Tanaka, Ryoji Sassa, Julie R. Ingelfinger, Toshiro Fujita, Masaomi Nangaku

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Reduction of vascular endothelial growth factor (VEGF) expression plays a crucial role in chronic kidney disease (CKD). In order to clarify a cause of VEGF suppression in CKD, we examined an interaction between proteinuria and VEGF. Rat proximal tubular cells were subjected to hypoxia with or without albumin to mimic proteinuric conditions, and VEGF expression was assessed by real-time quantitative PCR and enzyme-linked immunosorbent assays. Albumin significantly reduced VEGF expression under hypoxia. Luciferase activity controlled by hypoxia-responsive element (HRE) was suppressed by albumin, demonstrating suppression of the hypoxia-inducible factor (HIF)/HRE pathway. Studies utilizing a proteasome inhibitor and a prolyl hydroxylase inhibitor showed that mechanisms of HIF/HRE pathway suppression by albumin load did not involve degradation of HIF protein levels. Further, albumin did not change HIF mRNA levels. Our data, for the first time, suggest a clear 'link' between proteinuria and hypoxia, the two principal pathogenic factors for CKD progression.

Original languageEnglish
Pages (from-to)305-310
Number of pages6
JournalBiochemical and biophysical research communications
Volume367
Issue number2
DOIs
Publication statusPublished - 2008 Mar 7
Externally publishedYes

Keywords

  • Albumin
  • HIF
  • Hypoxia
  • Proteinuria
  • Proximal tubule
  • VEGF

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Albumin suppresses vascular endothelial growth factor via alteration of hypoxia-inducible factor/hypoxia-responsive element pathway'. Together they form a unique fingerprint.

Cite this