Expression of Hypoxia‐Inducible Factor‐1α in Human Periodontal Tissue

Abstract

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