Elucidation of the mechanisms of healthy kidney formation via nutrient sensing signals during the fetal period

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19721
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Baba Masaya 熊本大学, 病院, 助教 (10347304)
• Co-Investigator(Kenkyū-buntansha): 有馬 勇一郎 熊本大学, 国際先端医学研究機構, 特任准教授 (60706414)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 腎発生 / 胎生期 / 栄養状態

Outline of Final Research Achievements

This study aims to elucidate the effects of maternal nutrition on fetal kidney development and contribute to promoting healthy nephrogenesis. To this end, we conducted research using nephron progenitor cell-specific nutrient-sensing mechanism-deficient mice (FlcnKO mice) and a low birth weight model induced by maternal nutritional restriction during pregnancy. In low birth weight P0 mice, a reduction in the number of glomeruli was observed, supporting findings reported in humans. In FlcnKO P0 mice, a decrease in nephron progenitor cells, expansion of Bowman's capsule, and abnormalities in the loops of Henle were noted. Additionally, in the kidneys of FlcnKO mice, the nutrient-responsive transcription factor Tfe3 was localized in the nucleus, suggesting that abnormal activation of Tfe3 might contribute to kidney developmental abnormalities.

Free Research Field

泌尿器科

Academic Significance and Societal Importance of the Research Achievements

腎臓の機能単位であるネフロンは再生することがなく生理的な加齢と共に減少していく。その為、生涯にわたり腎臓の機能を良好に維持する為には、充分な数のネフロンを持った健全な腎臓を胎生期に形成する事が不可欠である。大規模な疫学調査により、胎生期における母体の低栄養が子供のネフロン数の減少と高い相関関係にあることが明らかにされており、胎生期の栄養と腎臓の発生の間には深い関係があることが示唆されてきた。母体の栄養制限で新生児のネフロン数が減少し、胎児の栄養感知機構のノックアウトがネフロン前駆細胞の減少を引き起こす事を見出した本研究は、母体からの栄養が胎児の腎発生に与える影響を明らかにする足がかりとなる。