Journal of periodontology
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Journal of periodontology · Sep 2013
Inhibition of transforming growth factor β1/Smad3 signaling decreases hypoxia-inducible factor-1α protein stability by inducing prolyl hydroxylase 2 expression in human periodontal ligament cells.
Hypoxia-inducible factor-1α (HIF-1α), the α subunit of the heterodimeric transcription factor HIF-1, maintains oxygen homeostasis by regulating gene expression. Under normoxic conditions, HIF-1α expression is maintained at low steady-state levels by the critical oxygen sensor prolyl hydroxylase 2 (PHD2). Transforming growth factor β1 (TGF-β1) activates Smad3 signaling and contributes to HIF-1α stabilization under normoxic conditions. In chronic periodontitis, HIF-1α is expressed highly in gingival fibroblasts and upregulates inflammatory factor transcription, which promotes periodontal inflammation. Here, the authors investigated the effect of TGF-β1/Smad3 signaling and its blockade by the specific inhibitor of Smad3 (SIS3) on HIF-1α expression and stability in human periodontal ligament cells. ⋯ These results demonstrate that HIF-1α transcription and protein synthesis are controlled by TGF-β1/Smad3 signaling, whereas HIF-1α protein stability is controlled by PHD2, which is regulated by TGF-β1/Smad3 signaling.