2023 Fiscal Year Final Research Report

Understanding of the pathobiochemical significance of prorenin, an early marker of diabetic complications: collaborative work between India, Bangladesh and Japan

Research Project

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Project/Area Number	18KK0273
Research Category	Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research Institution	Gifu University
Principal Investigator	Ebihara Akio 岐阜大学, 応用生物科学部, 教授 (60415099)
Co-Investigator(Kenkyū-buntansha)	寺本好邦京都大学, 農学研究科, 准教授 (40415716) 橋本美涼岐阜大学, 応用生物科学部, 助教 (80805424)
Project Period (FY)	2018-10-09 – 2024-03-31
Keywords	プロレニン / 糖尿病 / 糖尿病合併症 / 臨床現場即時検査法 / SDGs
Outline of Final Research Achievements	This study aims to develop a point-of-care testing for prorenin, an early marker of diabetic complications, and to investigate the pathobiochemical significance of prorenin in diabetes pathology through a collaboration between India, Bangladesh and Japan. We identified a new antibody pair that sandwiches the antigen prorenin and produced recombinant single-chain variable fragment that retains antigen recognition capability, even with a small molecular weight. We improved a prorenin measurement method based on renin enzymatic activity. Additionally, we found that non-coding single nucleotide variants of genes involved in renin-angiotensin-aldosterone system, which regulate blood pressure, may be significant risk factors for hypertension and type 2 diabetes-associated hypertension.
Free Research Field	酵素科学
Academic Significance and Societal Importance of the Research Achievements	見いだした新規抗体ペアと改良した酵素レニン活性に基づくプロレニン測定法を組み合わせ、正確性が裏打ちされ臨床現場で利用可能な感度と特異性をもつPOCTの作成に貢献できる。プロレニンを含む血圧調節系レニン・アンジオテンシン・アルドステロンの生体分子は心血管疾患の発症に関わる。糖尿病や高血圧症、心血管疾患がCOVID-19の重症化の危険因子であるとも報告されている。本研究で実施した集団遺伝学的アプローチによる糖尿病含む多因子遺伝疾患の危険因子探索とプロレニン濃度との相関解析は、プロレニンが関連する疾患の理解、ならびにSDGsのターゲット3.4「非感染性疾患による若年死亡率の減少」の達成につながる。