Elucidation of Regulatory Mechanism of Vitamin D- Vitamin D Receptor System in Cardiovascular Tissues in Uremic Milieu

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08598
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Showa University
• Principal Investigator: OGATA HIROAKI 昭和大学, 医学部, 教授 (30296959)
• Co-Investigator(Kenkyū-buntansha): 溝渕 正英 昭和大学, 医学部, 准教授 (90465203)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ビタミンD / ビタミンD受容体 / 尿毒勝 / CKD-MBD

Outline of Final Research Achievements

In CKD, disturbed the vitamin D (VD)-VD receptor (VDR) system due to impaired VD activation is involved in the high incidence of cardiovascular disease. However, resistance to exogenous vitamin D administration is clinically observed, and the mechanism remains unknown. In this study, FGF-23 exacerbated myocardial injury in a mouse model of cardiovascular injury, but calcitriol alleviated the injury. Interestingly, myocardial fibrosis was associated with Cyp27/Cyp24 expression in cardiomyocytes. These results suggest that local regulation of VD activation is important for the progression of myocardial injury. The balance between FGF-23 loading and VD activation may be important for cardiovascular protection by activated VD treatment.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

VD-VDR系活性化障害が関与する心血管組織傷害において、外因性VD製剤投与に対する治療抵抗性の存在が示唆されてきた。本研究によってのその抵抗性の機序の一端に外因性VD投与によりFGF-23発現が誘導され、局所のVD活性化障害、VD代謝が亢進し、VD-VDR系活性化が抑制されることが明らかになった。今後、VD-VDR系活性化障害が関与している心腎連関に対する新規治療法の開発に有用な知見である。