Elucidating the regulatory mechanisms of Prg4 expression by the formation of the transcriptional complex including Irx3 on its promoter
| Project/Area Number |
17K11636
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | The University of Tokushima (2018-2019)
Kyoto University (2017) |
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Principal Investigator |
TAMAMURA Yoshihiro 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (70431963)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Irx3 / Prg4 / TGFβ / Wnt / 軟骨細胞 / 関節軟骨 / promoter |
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| Outline of Final Research Achievements |
Prg4 is a secreted factor which is expressed in surface layer of articular cartilage. Although Prg4 has been reported to enhance the joint lubrication and inhibit the progression of cartilage degradation, regulatory mechanisms of its transcription are largely unknown. In this study, we showed that transcription factor Irx3 upregulates Prg4 expression by forming the transcriptional complex with TGF-beta-mediated Smad3 and Nfatc2 which is reported to repress osteoarthritis. We also reported the relationship between Irx3 and Wnt/beta-catenin signaling which is a major regulator of Prg4 expression. Irx3 increased not only the expression of Wnt4 and Wnt co-receptor Lgr6 but the transcriptional activity of Wnt signaling. These results indicate that Irx3 upregulates Prg4 expression by the interaction with TGF-beta or Wnt/beta-catenin signaling. Thus, Irx3 might be one of the clinical target for the treatment of cartilage degradation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の学術的意義は、Irx3の関節軟骨での発現を明らかにし、Prg4発現誘導シグナルであるTGFβやWntシグナルとの相互作用を介した新たなPrg4発現調節機構を解明したことである。Prg4は軟骨変性疾患の進行を阻止することが報告されており、本研究結果から、Prg4発現を上昇させるIrx3は同疾患の新たな治療標的となりえる可能性が示唆され、本研究は社会的意義が高いと考えられる。
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Report
(4 results)
Research Products
(6 results)
