Hypoxia upregulates VEGF expression in alveolar epithelial cells in vitro and in vivo. Academic Article uri icon

Overview

MeSH

  • Animals
  • Calcium Chloride
  • Cell Membrane Permeability
  • Cells, Cultured
  • Deferoxamine
  • Male
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Transcription, Genetic
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

MeSH Major

  • Anoxia
  • Cell Hypoxia
  • Endothelial Growth Factors
  • Gene Expression Regulation
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Pulmonary Alveoli
  • Respiratory Mucosa

abstract

  • We investigated regulation of vascular endothelial growth factor (VEGF) expression by hypoxia in cultured and freshly isolated rat alveolar epithelial cells (AEC). In vitro, hypoxia increased VEGF mRNA and protein levels, with maximal stimulation at 0% O2 for 18 h. A similar upregulation of VEGF expression was found in alveolar epithelial type II (ATII) cells freshly isolated from rats exposed to 8% O2 for 24 h. In vitro, hypoxia-induced upregulation of VEGF mRNA was due to an increase in transcription, rather than an increase in RNA stability, inasmuch as the half-life of VEGF mRNA was unchanged. Upregulation of VEGF mRNA by hypoxia was mimicked by CoCl2 and desferrioxamine in normoxic AEC and was not prevented by inhibitors of reactive oxygen species, suggesting that hypoxic VEGF regulation involved an O2-dependent protein that requires ferrous ions but is independent of reactive oxygen species generation. In polarized ATII cells, VEGF protein was secreted at the apical and basolateral sides. Similarly, in rats, VEGF was secreted in bronchoalveolar lavage fluid. Hypoxia induced a twofold increase in VEGF protein at the apical side of ATII cells in culture and in bronchoalveolar lavage fluid. These findings suggest that release of VEGF synthesized by AEC may target not only endothelial cells but also other alveolar cells, including macrophages and epithelial cells.

publication date

  • November 2002

has subject area

  • Animals
  • Anoxia
  • Calcium Chloride
  • Cell Hypoxia
  • Cell Membrane Permeability
  • Cells, Cultured
  • Deferoxamine
  • Endothelial Growth Factors
  • Gene Expression Regulation
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Male
  • Pulmonary Alveoli
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Mucosa
  • Transcription, Genetic
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00464.2001

PubMed ID

  • 12376368

Additional Document Info

start page

  • L1133

end page

  • L1142

volume

  • 283

number

  • 5