The effects of epigenetic modification on the pathogenesis and the development of chronic kidney disease

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H05061
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: The University of Tokushima
• Principal Investigator: MASUDA Masashi 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (50754488)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: FGF23

Outline of Final Research Achievements

In this study, we investigated the relationship between the increased plasma retinol levels in chronic kidney disease (CKD) and the epigenetic modification of fibroblast growth factor 23 (FGF23) gene. From the experiment of the administration of all-trans retinoic acid (ATRA) and retinoic acid receptor (RAR)-selective antagonists to CKD model mice, we suggested that ATRA may alleviate elevated plasma FGF23 levels through RARγ in CKD. In addition, lucifearase assay indicated that histone deacetylase (HDAC) may get involved in the depression effect of RA on the FGF23 gene promoter activity through RARγ.
Together, these results suggest that retinol may contribute to the alleviation of the abnormal elevation of plasma FGF23 levels in CKD.

Free Research Field

慢性腎臓病

Academic Significance and Societal Importance of the Research Achievements

わが国の慢性腎臓病（CKD）患者は年々増加傾向で、CKDは新たな「国民病」とも言われている。CKDになると腎臓でのリン調節機構の破綻による高リン血症や異常なFGF23の上昇が、骨病変・血管石灰化等の骨ミネラル代謝異常（CKD-MBD）や筋萎縮・脂肪減少等のタンパク質－エネルギー障害（CKD-PEW）への発展に寄与することが考えられている。本研究成果は、CKD発症・進行だけでなく、CKDに付随して起こる様々な障害の理解につながり、CKDの新規予防・治療法確立にとって大きな一歩となった。また、エピゲノム変化に関しては未だ不明な点が多く、本研究成果がエピゲノム研究発展の一助となることが期待される。