| http://purl.uniprot.org/citations/23088526 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23088526 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundHypoxia-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.MethodsThe authors investigated the effect of TGF-β1 on HIF-1α protein stability using cycloheximide. Furthermore, they analyzed HIF-1α expression, PHD2 expression, and Smad3 phosphorylation following TGF-β1 stimulation in the presence or absence of SIS3.ResultsThe half-life of HIF-1α was prolonged in TGF-β1-treated cells. TGF-β1 treatment induced HIF-1α gene expression and enhanced HIF-1α protein stability while decreasing PHD2 expression and activating Smad3 phosphorylation. Notably, HIF-1α protein expression was not detectable prior to TGF-β1 stimulation. Furthermore, SIS3 treatment abrogated Smad3 phosphorylation, impaired TGF-β1-induced HIF-1α gene expression and protein stability, and stimulated TGF-β1-mediated PHD2 inhibition.ConclusionThese 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."xsd:string |
| http://purl.uniprot.org/citations/23088526 | http://purl.org/dc/terms/identifier | "doi:10.1902/jop.2012.120373"xsd:string |
| http://purl.uniprot.org/citations/23088526 | http://purl.uniprot.org/core/author | "Watanabe T."xsd:string |
| http://purl.uniprot.org/citations/23088526 | http://purl.uniprot.org/core/author | "Tanaka E."xsd:string |
| http://purl.uniprot.org/citations/23088526 | http://purl.uniprot.org/core/author | "Yasue A."xsd:string |
| http://purl.uniprot.org/citations/23088526 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23088526 | http://purl.uniprot.org/core/name | "J Periodontol"xsd:string |
| http://purl.uniprot.org/citations/23088526 | http://purl.uniprot.org/core/pages | "1346-1352"xsd:string |
| http://purl.uniprot.org/citations/23088526 | http://purl.uniprot.org/core/title | "Inhibition of transforming growth factor beta1/Smad3 signaling decreases hypoxia-inducible factor-1alpha protein stability by inducing prolyl hydroxylase 2 expression in human periodontal ligament cells."xsd:string |
| http://purl.uniprot.org/citations/23088526 | http://purl.uniprot.org/core/volume | "84"xsd:string |
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