The mechanism of chronic pain in Ehlers-Danlos syndrome caused by tenascin-X deficiency
| Project/Area Number |
17K08271
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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 |
Biological pharmacy
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| Research Institution | Shimane University |
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Principal Investigator |
Sakai Hiromichi 島根大学, 学術研究院医学・看護学系, 助教 (00375255)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | エーラス・ダンロス症候群 / 慢性疼痛 / テネイシンX / ジアシルグリセロールキナーゼ / 坐骨神経 / 筋肉 / 細胞増殖 / 関節 / 筋分化 / 増殖 / 細胞外マトリックス |
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| Outline of Final Research Achievements |
Ehlers-Danlos syndrome (EDS) patients frequently complain of chronic pain. Tenascin-X (TNX) is known as one of causative genes for EDS. In this study, we observed that the number of blood vessels in sciatic nerves of TNX-deficient mice was significantly decreased. However, the levels of HIF-1α, which is a marker of hypoxia, was not altered, indicating that hypoxia for pain might be not induced in TNX-deficient mice. On the other hand, it is thought that chronic pain in muscle is caused by the reduction of capability of muscle regeneration. To explore the mechanism, we showed that diacylglycerol kinase η might regulate myoblast proliferation, which is an important for muscle regeneration, through mTOR complex 1-fatty acid synthase pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝性結合組織疾患エーラス・ダンロス症候群（EDS）は，患者の関節や筋肉に慢性疼痛をもたらし，著しくクオリティー・オブ・ライフ（QOL）を低下させる．従って，EDS患者のQOLを向上させるためには，慢性疼痛の発生メカニズムを解明し，新たに治療法を開発することが重要である．本研究により，ジアシルグリセロールキナーゼη（DGKη）は筋芽細胞の増殖を制御することを示した．従って，今後，このDGKηがどのようにEDS患者の筋再生に寄与するのかを明らかにすることが，慢性疼痛の発生メカニズムを解明する上で重要である．
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] A potential contribution of tenascin-X to blood vessel formation in peripheral nerves.2017
Author(s)
Sakai, H., Yokota, S., Kajitani, N., Yoneyama, T., Kawakami, K., Yasui, Y., Matsumoto, KI.
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Journal Title
Neurosci. Res.
Volume: 124
Pages: 1-7
DOI
Related Report
Peer Reviewed / Open Access
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