The mechanism of chronic pain in Ehlers-Danlos syndrome caused by tenascin-X deficiency

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08271
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Shimane University
• Principal Investigator: Sakai Hiromichi 島根大学, 学術研究院医学・看護学系, 助教 (00375255)
• Project Period (FY): 2017-04-01 – 2020-03-31
• 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

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.

Free Research Field

病態生化学

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．