Periostin inhibits hypoxia-induced apoptosis in human periodontal ligament cells via TGF-β signaling. 2013

Paveenarat Aukkarasongsup, and Naoto Haruyama, and Tsutomu Matsumoto, and Momotoshi Shiga, and Keiji Moriyama
Section of Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.

Periostin (POSTN) is an extracellular matrix protein expressed predominantly in periodontal ligament (PDL) cells. The aim of this study was to investigate the effects of POSTN on human PDL cell apoptosis under hypoxic conditions. The percentage of apoptotic PDL cells under hypoxia was increased significantly when the endogenous POSTN gene was silenced using siRNA, but decreased when cells were treated with recombinant human POSTN (rhPOSTN), or when mouse Postn was overexpressed in vitro. Silencing POSTN during hypoxia decreased the expression of HIF prolyl-hydroxylase 2 (PHD2), but increased HIF-1α protein level. Conversely, treating hypoxic cells with rhPOSTN or overexpressing Postn increased PHD2 expression but decreased HIF-1α levels. The addition of rhPOSTN in the absence of a TGF-β receptor inhibitor (SB525334) significantly decreased hypoxia-induced apoptosis, while the effects of rhPOSTN were abolished when cells were co-treated with SB525334. Consistent with this, the phosphorylation of SMAD2 was increased in hypoxic PDL cells by the knockdown of POSTN, but decreased by treatment with rhPOSTN. Under normoxia, the PHD2 expression, HIF-1α level, and apoptosis were unaffected by POSTN siRNA, rhPOSTN, or Postn overexpression. These findings suggest that, under hypoxic conditions, POSTN regulates PHD2 expression and HIF-1α levels by modulating TGF-β1 signaling, leading to decreased apoptosis.

UI MeSH Term Description Entries
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D010513 Periodontal Ligament The fibrous CONNECTIVE TISSUE surrounding the TOOTH ROOT, separating it from and attaching it to the alveolar bone (ALVEOLAR PROCESS). Alveolodental Ligament,Alveolodental Membrane,Gomphosis,Alveolodental Ligaments,Alveolodental Membranes,Gomphoses,Ligament, Alveolodental,Ligament, Periodontal,Membrane, Alveolodental,Periodontal Ligaments
D011518 Proto-Oncogene Proteins Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015687 Cell Hypoxia A condition of decreased oxygen content at the cellular level. Anoxia, Cellular,Cell Anoxia,Hypoxia, Cellular,Anoxia, Cell,Anoxias, Cell,Anoxias, Cellular,Cell Anoxias,Cell Hypoxias,Cellular Anoxia,Cellular Anoxias,Cellular Hypoxia,Cellular Hypoxias,Hypoxia, Cell,Hypoxias, Cell,Hypoxias, Cellular

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