Paracrine upregulation of VEGF receptor mRNA in endothelial cells by hypoxia-exposed Hep G2 cells

Hidekazu Suzuki, Koichi Seto, Yuichi Shinoda, Mikiji Mori, Yuzuru Ishimura, Makoto Suematsu, Hiromasa Ishii

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Although vascular endothelial growth factor (VEGF) plays a role in the growth of hypervascular tumors, mechanisms for paracrine regulation of its receptor expression on vascular endothelial cells remain unknown. This study aimed to investigate whether VEGF released from hypoxia-exposed Hep G2 cells alters expression of the two distinct receptors, kinase insert domain- containing receptor (KDR) and fms-like tyrosine kinase 1 (fit-1), in human umbilical venous endothelial cells (HUVEC). Hep G2 cells were cultured in 20% or 1% O2 for 16 h to examine induction of VEGF mRNA and its protein expression. Conditioned medium from Hep G2 cells (CM) was applied to HUVEC under normoxic conditions, and expression of mRNA for the VEGF receptors was determined by RT-PCR. In response to the hypoxic challenge, Hep G2 cells upregulated VEGF mRNA and the release of VEGF. Hypoxia-CM preferentially stimulated the mRNA expression of flt-1 but not that of KDR in HUVEC. When the VEGF release from hypoxia-exposed Hep G2 cells was blocked by its antisense oligodeoxynucleotide, the endothelial flt-1 mRNA upregulation elicited by the hypoxia-CM was still maintained. These results suggest that hypoxia-exposed Hep G2 cells not only produce VEGF but also evolve paracrine induction of flt-1 through VEGF-independent mechanisms.

Original languageEnglish
Pages (from-to)G92-G97
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume276
Issue number1 39-1
DOIs
Publication statusPublished - 1999 Jan

Keywords

  • Antisense oligodeoxynucleotide
  • Flt-1
  • Kinase insert domain-containing receptor
  • Reverse transcription-polymerase chain reaction

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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