Involvement of enteric mineralocorticoid receptor in the pathogenesis of diabetic nephropathy.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08713
• 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: Keio University
• Principal Investigator: Kurihara Isao 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (90338038)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ミネラルコルチコイド受容体 / 腸管 / 糖代謝

Outline of Final Research Achievements

We recently demonstrated that enteric mineralocorticoid receptor (MR) has a pivotal role in blood pressure regulation through Na uptake in the gut by using enterocyte-specific MR deficient mice, which were originally developed in our research group. In this study, we used the same animal model to elucidate a novel function of enteric MR on glucose metablism and its related comorbidities including diabetic nephropathy. In the microarray analysis using the intestinal tissues derived from this model, some of the factors related with glucose metabolism had altered expression, but we could not demonstrate the involvement of enteric MR in the pathogenesis of certain metabolic disorders. Then we developed enterocyte-specific Casz1 deficient mice, in which enteric MR is aberrantly activated because Casz1 is a newly-identified corepressor of MR, to conduct further analyses for this unanswerd issue.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

現在、日常診療において降圧薬として使用されているMR拮抗薬は、高血圧に対してのみならず、心不全や糖尿病性腎症の予後改善効果など多くの病態において、その有益性が大規模臨床研究によって示されている。中でも、末期腎不全患者におけるMR拮抗薬の有益性は特筆すべき知見であり、MR拮抗薬が、腎臓MRだけでなく、腸管MRをも介してその有益性をもたらしている可能性が推察される。これまで、各種疾患における腸管MRの関与については、ほとんど注目されておらず、本研究の成果は、病態解明において新たな視点を与え、各種疾患、特に糖代謝疾患における新規治療アプローチの開発へ、有用な知見をもたらしてくれることが期待される。