Hypoxia-induced upregulation of angiogenic factors in immortalized human periodontal ligament fibroblasts

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Author(s)

    • Kifune Takashi
    • Department of Pediatric Dentistry, Nihon University School of Dentistry
    • Ito Hisanori
    • Department of Pediatric Dentistry, Nihon University School of Dentistry
    • Ishiyama Misa
    • Department of Pediatric Dentistry, Nihon University School of Dentistry
    • Iwasa Satoko
    • Department of Pediatric Dentistry, Nihon University School of Dentistry
    • Takei Hiroki
    • Department of Pediatric Dentistry, Nihon University School of Dentistry
    • Shirakawa Tetsuo
    • Department of Pediatric Dentistry, Nihon University School of Dentistry|Division of Oral and Craniomaxillofacial Research, Dental Research Center, Nihon University School of Dentistry

Abstract

<p>Hypoxia induces complex cellular responses that are mediated by a key transcription factor, hypoxia-inducible factor-1 (HIF-1). HIF-1 promotes production of cytokines and angiogenic factors and contributes to recovery of injured tissues. In the present study, expressions of angiogenin (ANG) and vascular endothelial growth factor (VEGF), which are potent angiogenic factors in mammalian tissues, were examined in immortalized fibroblasts exposed to hypoxia. After 24 h of exposure to hypoxia, ANG and VEGF mRNAs expressions were significantly elevated in periodontal ligament (PDL) fibroblasts but not in embryonic fibroblasts. Hypoxia also increased productions of ANG and VEGF proteins in PDL fibroblasts. HIF-1α mRNA expression was not affected by hypoxia in either fibroblast, although HIF-1α protein expression was enhanced after exposure to hypoxia. Treatment of PDL fibroblasts with dimethyloxaloylglycine, a prolyl hydroxylase inhibitor that stabilizes the HIF-1α protein, significantly increased expressions of ANG and VEGF mRNAs under normoxia. This suggests that stabilization of HIF-1α is crucial for upregulation of ANG and VEGF in PDL fibroblasts. These results indicate that, under hypoxic conditions, HIF-1α upregulates synthesis of ANG and VEGF in PDL fibroblasts and promotes angiogenesis.</p>

Journal

  • Journal of Oral Science

    Journal of Oral Science 60(4), 519-525, 2018

    Nihon University School of Dentistry

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