Study on biomarker of kidney injury therapy and its regulation mechanism

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08682
• 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: University of Shizuoka
• Principal Investigator: Mori Kiyoshi 静岡県立大学, 薬学部, 特任教授 (60343232)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 急性腎障害 / バイオマーカー / NGAL

Outline of Final Research Achievements

Neutrophil gelatinase-associated lipocalin (NGAL) is an iron carrier protein whose circulating level is increased by kidney injury, bacterial infection and obesity, but its metabolic consequence remains elusive. To clarify the physiological role of NGAL in energy homeostasis, wild-type and NGAL-deficient mice were subjected to a high-fat diet or cold exposure. NGAL-deficient mice showed exhibited larger brown adipose tissues (BAT) and gained less body weights as compared to WT mice. These data suggest that endogenous NGAL negatively regulated the sympathetic nervous system and thermogenesis. When exposed to cold condition, KO mice showed higher body temperature and more intense 18F-fluorodeoxyglucose uptake in BAT, which were cancelled by adrenergic receptor blocker. These results suggest that NGAL possesses anti-thermogenic effects through inhibition of BAT activity.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

以上の結果より、NGALは交感神経の制御によりエネルギー代謝を抑制的に働いていることが考えられる。さらに尿中NGALについて、脳外科手術後、突然発症した急性膵炎による乏尿性AKIにおいても、早期の尿中NGAL上昇は軽度で、腎実質性AKIを除外し大量輸液を行う判断に有用であった症例や、また免疫チェックポイント阻害薬を用いたがん治療を行った場合に、副作用として急性尿細管間質性腎炎が起こるこの病態において、尿中NGALが上昇し、ステロイド治療により低下した2症例について報告しており、臨床におけるNGALの意義を示唆している。