Expression of hypoxia-inducible factor-1α in human periodontal tissue

J Periodontol. 2011 Jan;82(1):136-41. doi: 10.1902/jop.2010.100100. Epub 2010 Nov 2.

Abstract

Background: Hypoxia-inducible factor (HIF)-1 is a key transcription factor responding to hypoxia. It is composed of an oxygen-sensitive α subunit (HIF-1α) and a constitutively expressed β subunit. Increasing evidence indicates an essential role for HIF-1α in infection and immunity. Because inflamed periodontium is thought to be hypoxic, we hypothesize that HIF-1α is expressed and related to its upstream regulator tumor necrosis factor (TNF)-α and downstream effecter vascular endothelial growth factor (VEGF).

Methods: Human gingival biopsies were collected from advanced periodontitis sites and clinically healthy sites, and immunohistochemically examined for HIF-1α and VEGF peptides. The messenger ribonucleic acid (mRNA) and protein levels of HIF-1α, VEGF, and TNF-α in the biopsies were then assessed by reverse transcription polymerase chain reaction and Western blotting.

Results: HIF-1α-positive immunoreactivity was detected in the nuclei of epithelial and endothelial cells. In periodontal pockets, there was a marked increase in the proportion of fibroblast-like cells and leukocyte-like cells expressing HIF-1α. Protein levels of HIF-1α, VEGF, and TNF-α were significantly higher in periodontal pockets than in control gingival samples. The mRNA expression of VEGF and TNF-α was also increased in periodontal pockets.

Conclusion: HIF-1α is expressed in healthy and diseased periodontium and may be related to TNF-α and VEGF function during periodontitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aryl Hydrocarbon Receptor Nuclear Translocator / analysis
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Chronic Periodontitis / metabolism
  • Chronic Periodontitis / pathology*
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Gingiva / metabolism
  • Gingiva / pathology
  • Humans
  • Hypoxia-Inducible Factor 1 / analysis*
  • Hypoxia-Inducible Factor 1, alpha Subunit / analysis
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Middle Aged
  • Periodontal Pocket / metabolism
  • Periodontal Pocket / pathology
  • Periodontium / metabolism
  • Periodontium / pathology*
  • Tumor Necrosis Factor-alpha / analysis
  • Vascular Endothelial Growth Factor A / analysis

Substances

  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Aryl Hydrocarbon Receptor Nuclear Translocator