Periostin Associates with Notch1 Precursor to Maintain Notch1 Expression under a Stress Condition in Mouse Cells |
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| Authors: | Hideyuki Tanabe Issei Takayama Takashi Nishiyama Masashi Shimazaki Isao Kii Minqi Li Norio Amizuka Ken-ichi Katsube Akira Kudo |
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| Institution: | 1. Department of Biological Information, Tokyo Institute of Technology, Yokohama, Japan.; 2. Division of Oral Health Science, Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.; 3. Department of Molecular Pathology, Graduate School of Tokyo Medical and Dental University, Tokyo, Japan.;Universität Heidelberg, Germany |
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| Abstract: | BackgroundMatricellular proteins, including periostin, modulate cell-matrix interactions and cell functions by acting outside of cells.Methods and FindingsIn this study, however, we reported that periostin physically associates with the Notch1 precursor at its EGF repeats in the inside of cells. Moreover, by using the periodontal ligament of molar from periostin-deficient adult mice (Pn−/− molar PDL), which is a constitutively mechanically stressed tissue, we found that periostin maintained the site-1 cleaved 120-kDa transmembrane domain of Notch1 (N1™) level without regulating Notch1 mRNA expression. N1™ maintenance in vitro was also observed under such a stress condition as heat and H2O2 treatment in periostin overexpressed cells. Furthermore, we found that the expression of a downstream effector of Notch signaling, Bcl-xL was decreased in the Pn−/− molar PDL, and in the molar movement, cell death was enhanced in the pressure side of Pn−/− molar PDL.ConclusionThese results suggest the possibility that periostin inhibits cell death through up-regulation of Bcl-xL expression by maintaining the Notch1 protein level under the stress condition, which is caused by its physical association with the Notch1 precursor. |
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