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


CONCLUSIONS
HIF-1α is expressed in healthy and diseased periodontium and may be related to TNF-α and VEGF function during periodontitis.
Department of Physiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
King-Tung
KT
Ng
Jing-Ping
JP
Li
Kwong Man
KM
Ng
George L
GL
Tipoe
W Keung
WK
Leung
Man-Lung
ML
Fung
D000328:Adult; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000032:analysis; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D055113:Chronic Periodontitis / Q000378:metabolism / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005881:Gingiva / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000032:analysis*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D010514:Periodontal Pocket / Q000378:metabolism / Q000473:pathology; D010519:Periodontium / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator