Rare Diseases Symptoms Automatic Extraction

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

[oral submucous fibrosis]

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.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.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).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.

Diseases presenting "wide variety" symptom

  • alexander disease
  • allergic bronchopulmonary aspergillosis
  • cadasil
  • erythropoietic protoporphyria
  • esophageal carcinoma
  • familial hypocalciuric hypercalcemia
  • gm1 gangliosidosis
  • junctional epidermolysis bullosa
  • lamellar ichthyosis
  • lymphangioleiomyomatosis
  • oral submucous fibrosis
  • pleomorphic liposarcoma
  • proteus syndrome
  • severe combined immunodeficiency
  • x-linked adrenoleukodystrophy
  • zellweger syndrome

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