Research of EDA and its associated molecules

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09037
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Awazawa Motoharu 国立研究開発法人国立国際医療研究センター, その他部局等, 糖尿病研究センター 分子糖尿病医学研究部 統合生理学研究室長 (90466764)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: EDA / 皮膚 / 代謝 / 肥満 / 熱放散 / シングルセル解析

Outline of Final Research Achievements

We performed the activation of EDA-A1 signaling by EDAR-stimulated antibodies and investigated its effects on metabolism. We also analyzed a model of EDA-A1-specific overexpression in the liver through AAV administration. Unfortunately, however, no significant changes in metabolic phenotype were observed, although blood glucose levels tended to increase. As a further step, we investigated the relationships between skin and metabolism in a broader perspective through investigating different models. Interventions on skin heat dissipation through topical application of PGI2 analogue had an effect on systemic metabolism. Single-cell gene analysis of skin from obese mouse models revealed changes in gene expression in various cell groups compared to lean control mouse skin, some of which were observed in the genes related to inflammation and systemic heat production.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

EDAという皮膚関連分子が肥満成人の肝臓において発現増加を示すことを端緒に研究を進め、より広い意味で肥満状態においては皮膚の分子生物学的性質変化が生じうること、さらにまたそうした皮膚の機能変化が、実際に全身の代謝に対して影響を持ちうることを初めて示した。これまでの代謝研究では皮膚は糖尿病の合併症臓器として捉えられることが常であったが、本研究に基づき皮膚が全身の代謝制御に積極的な役割を果たしている可能性が提示され、今後の発展的研究を進めるための根拠が得られた。