Hypoxic regulation of plasminogen activator inhibitor-1 expression in human buccal mucosa fibroblasts stimulated with arecoline.

Abstract

BACKGROUND:

Oral submucous fibrosis (OSF) is regarded as a pre-cancerous condition with fibrosis in oral subepithelial connective tissue. Hypoxia-inducible factor (HIF)-1α regulates a wide variety of profibrogenic genes, which are closely associated with tissue fibrosis. The aim of this study was to compare HIF-1α expression in normal buccal mucosa tissues and OSF specimens and further explore the potential mechanisms that may lead to the induction of HIF-1α expression.

METHOD:

Twenty-five OSF specimens and six normal buccal mucosa were examined by immunohistochemistry. The expression of HIF-1α from fibroblasts cultured from OSF and normal buccal mucosa was measured by Western blot. Arecoline, a major areca nut alkaloid, was challenged to normal buccal mucosa fibroblasts (BMFs) to elucidate whether HIF-1α expression could affect by arecoline. In addition, the effects of arecoline on plasminogen activator inhibitor (PAI)-1 expression were evaluated in environmental hypoxia.

RESULTS:

HIF-1α expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, epithelial cells, and inflammatory cells. Fibroblasts derived from OSF were found to exhibit higher HIF-1α protein expression than BMFs (P < 0.05). Arecoline was found to upregulate HIF-1α protein in a dose-dependent manner (P < 0.05). Hypoxia increased arecoline-induced PAI-1 protein expression than normoxic conditions (P < 0.05).

CONCLUSION:

These results suggest that HIF-1α expression is significantly upregulated in OSF tissues from areca quid chewers, implying a potential role as a biomarker for local tissue hypoxia. The activation of HIF-1α may promote fibrogenesis by an increase of PAI-1 expression and a subsequent elevation of extracellular matrix production in oral submucosa leading to fibrosis.

• Authors: Chung-Hung Tsai, Shiuan-Shinn Lee, Yu-Chao Chang
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 44 Issue 9 Pg. 669-73 (Oct 2015) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 25367145 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• Hypoxia-Inducible Factor 1, alpha Subunit
• Plasminogen Activator Inhibitor 1
• SERPINE1 protein, human
• Arecoline

Topics

• Arecoline (pharmacology)
• Biomarkers (metabolism)
• Cell Hypoxia (physiology)
• Cells, Cultured
• Connective Tissue (drug effects, metabolism)
• Epithelial Cells (cytology, drug effects, metabolism)
• Fibroblasts (cytology, drug effects, metabolism)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (biosynthesis)
• Immunohistochemistry
• Male
• Mouth Mucosa (cytology, drug effects, metabolism)
• Oral Submucous Fibrosis (drug therapy, pathology)
• Plasminogen Activator Inhibitor 1 (biosynthesis)
• Up-Regulation (drug effects)