Regulated expression of hypoxia-inducible factors during postnatal and postpneumonectomy lung growth

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27 Scopus citations

Abstract

We previously found increased expression of erythropoietin receptor (EPO-R) in peripheral dog lung during postnatal and postpneumonectomy (PNX) lung growth. To study the upstream regulation of EPO-R, we analyzed the expression of hypoxia-inducible factors (HIF)-1α, -2α, and -3α during postnatal lung growth in immature and mature (2.5 and 12 mo old, respectively) dogs and during compensatory lung growth 3 wk and 10 mo after right PNX. Relative to their respective controls, HIF-1α transcript was 52-95% higher in immature lungs and 284% higher in the remaining lung 3 wk post-PNX. HIF-2α transcript did not change during maturation but was 42% lower 3 wk post-PNX. HIF-3α transcript was 53-65% lower in both the immature lung and 3 wk post-PNX. Changes were no longer detectable 10 mo post-PNX. No change in HIF transcripts was observed in kidney and liver post-PNX. Consistent with the mRNA changes, HIF-1α protein was 120 and 196% higher in growing lungs and 3 wk post-PNX relative to their respective controls. Overexpression of HIF-1α in cultured HEK-293 cells increased endogenous expression of EPO-R protein. These results demonstrate regulated expression of the HIF system and parallel changes in HIF-1α and EPO-R expression during two types of lung growth. Because the normal growing lung is not hypoxic, the HIF system likely responds to other signals encountered during sustained lung strain.

Original languageEnglish (US)
Pages (from-to)L880-L889
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume290
Issue number5
DOIs
StatePublished - May 1 2006

Keywords

  • Hypoxia-inducible factors
  • Immunoblot
  • Lung growth
  • Pneumonectomy
  • Postnatal development
  • Real-time polymerase chain reaction
  • Ribonucleic acid blot

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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