Elucidation of mechanisms of molecular recognition and sorting for normal from damaged albumin molecules in renal proximal tubules.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K11540
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Toho University
• Principal Investigator: Odera Keiko 東邦大学, 薬学部, 助教 (70453850)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 老化 / 食事制限 / 腎臓 / タンパク尿

Outline of Final Research Achievements

In this study, we found that abnormally modified (carbonylated, AGE-, CML-) albumin accumulated in the renal proximal tubular cells (RPTC) of old rats. These results suggest that the ability of abnormal albumin sorting and degradation was decreased with age. We also found that dietary restriction (DR) initiated from even old age reduced the amount of abnormal proteins in the kidney. However, no significant effect of DR was observed in the degradation rate of albumin and the amount of abnormal albumin in the kidney. In contrast, the ability of albumin uptake by RPTC in vivo tended to increase in old DR rats compared with old control ones. These results suggest that the improvement of albuminuria by DR may be due to the activation of reabsorption of normal albumin in primary urine. Future studies should be elucidated the intracellular behavior of abnormal albumin in RPTC.

Free Research Field

基礎老化学

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病患者に対し、腎臓病の進行を遅らせるために、タンパク質制限による食事療法が行われる。これは、窒素代謝物排泄などによる腎臓への負担軽減を目指したものである。腎臓病患者に対するタンパク質制限の臨床研究は、タンパク摂取量の継続的な管理の難しさ、合併症や薬物療法の有無、年齢などの様々な要因が複雑に絡み合うためにタンパク質制限の効果の明確なエビデンスがないのが現状である。本研究は、ラットを用いた基礎研究ではあるが、平日隔日食餌制限老齢ラットのアルブミントランスサイトーシスの活性化機構が明らかになれば、タンパク尿の予防法や治療法の提案に繋がると考えられる。