Mechanical Stress Activates Smad Pathway through PKCδ to Enhance Interleukin-11 Gene Transcription in Osteoblasts
| العنوان: | Mechanical Stress Activates Smad Pathway through PKCδ to Enhance Interleukin-11 Gene Transcription in Osteoblasts |
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| المؤلفون: | Daisuke Inoue, Toshio Matsumoto, Shinsuke Kido, Yasumichi Inoue, Hisaaki Taniguchi, Itsuro Endo, Yuka Umino-Miyatani, Takeshi Imamura, Rika Kuriwaka-Kido |
| المصدر: | PLoS ONE PLoS ONE, Vol 5, Iss 9, p e744 (2010) |
| بيانات النشر: | Public Library of Science, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Small interfering RNA, Transcription, Genetic, lcsh:Medicine, Smad Proteins, SMAD, Biology, Diabetes and Endocrinology/Bone and Mineral Metabolism, Cell Biology/Cell Signaling, Cell Line, Mice, medicine, Animals, Humans, Phosphorylation, lcsh:Science, Protein kinase C, Cells, Cultured, Multidisciplinary, Osteoblasts, lcsh:R, Promoter, Osteoblast, Transfection, Cell Biology, Interleukin-11, Molecular biology, Protein Kinase C-delta, medicine.anatomical_structure, Bone Morphogenetic Proteins, lcsh:Q, Stress, Mechanical, Signal transduction, Research Article, Protein Binding, Signal Transduction |
| الوصف: | Background Mechanical stress rapidly induces ΔFosB expression in osteoblasts, which binds to interleukin (IL)-11 gene promoter to enhance IL-11 expression, and IL-11 enhances osteoblast differentiation. Because bone morphogenetic proteins (BMPs) also stimulate IL-11 expression in osteoblasts, there is a possibility that BMP-Smad signaling is involved in the enhancement of osteoblast differentiation by mechanical stress. The present study was undertaken to clarify whether mechanical stress affects BMP-Smad signaling, and if so, to elucidate the role of Smad signaling in mechanical stress-induced enhancement of IL-11 gene transcription. Methodology/Principal Findings Mechanical loading by fluid shear stress (FSS) induced phosphorylation of BMP-specific receptor-regulated Smads (BR-Smads), Smad1/5, in murine primary osteoblasts (mPOBs). FSS rapidly phosphorylated Y311 of protein kinase C (PKC)δ, and phosphorylated PKCδ interacted with BR-Smads to phosphorylate BR-Smads. Transfection of PKCδ siRNA or Y311F mutant PKCδ abrogated BR-Smads phosphorylation and suppressed IL-11 gene transcription enhanced by FSS. Activated BR-Smads bound to the Smad-binding element (SBE) of IL-11 gene promoter and formed complex with ΔFosB/JunD heterodimer via binding to the C-terminal region of JunD. Site-directed mutagenesis in the SBE and the AP-1 site revealed that both SBE and AP-1 sites were required for full activation of IL-11 gene promoter by FSS. Conclusions/Significance These results demonstrate that PKCδ-BR-Smads pathway plays an important role in the intracellular signaling in response to mechanical stress, and that a cross-talk between PKCδ-BR-Smads and ΔFosB/JunD pathways synergistically stimulates IL-11 gene transcription in response to mechanical stress. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ffc80a37f06fb7e5c721ebc053301703Test http://europepmc.org/articles/PMC2947522Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ffc80a37f06fb7e5c721ebc053301703 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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