Significance of urinary megalin excretion linked to the pathophysiology of obesity- or metabolic syndrome-related nephropathy

• Project/Area Number: 17K09690
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Niigata University
• Principal Investigator: Hosojima Michihiro 新潟大学, 医歯学総合研究科, 特任准教授 (50464003)
• Co-Investigator(Kenkyū-buntansha): 斎藤 亮彦 新潟大学, 医歯学総合研究科, 特任教授 (80293207)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: メガリン / 糖尿病性腎症 / 肥満関連腎症 / バイオマーカー / 尿中メガリン

Outline of Final Research Achievements

Megalin, which is expressed in proximal tubular cells of the kidney, constitutes a renal “gateway” for nephrotoxic substances, being involved in the development of obesity- or metabolic syndrome-related nephropathy and diabetic nephropathy. In this study, we have established novel ELSIA systems to measure urinary A- (extracellular domain type) and C-megalin (full-length type) in mice. In the future, these technologies will contribute greatly to the basic research on megalin. In addition, our study in patients with type 2 diabetes has shown that urinary A- and C-megalin are novel biomarkers different from existing ones. Measuring both forms of urinary megalin in patients with diabetic nephropathy would enable us to predict future progression of the disease.

Academic Significance and Societal Importance of the Research Achievements

透析患者の増大は個々の患者の生活レベルの低下をもたらすだけでなく、医療経済上も重大な課題となっている。特に、糖尿病性腎症は透析療法導入の原因疾患の第一位を占めており、社会的にも喫緊の対応が求められている。中でも、その早期診断や重症度判定は重要な課題の1つであるが、病因や病態に基づいた新しいバイオマーカーの開発が求められていた。本研究では、尿中A-およびC-メガリンは既存のものとは異なる新規のバイオマーカーであることが示され、将来の糖尿病性腎症の進展を予測できることが明らかになった。今回開発したマウス尿中メガリン測定系を用いた今後の更なる研究の進展も期待される。

Research Products

• [Journal Article] Urinary A- and C-megalin predict progression of diabetic kidney disease : an exploratory retrospective cohort study (2022)
  • Author(s): Iida Tomomichi、Hosojima Michihiro、Kabasawa Hideyuki、Yamamoto-Kabasawa Keiko、Goto Sawako、Tanaka Takahiro、Kitamura Nobutaka、Nakada Mitsutaka、Itoh Shino、Ogasawara Shinya、Kaseda Ryohei、Suzuki Yoshiki、Narita Ichiei、Saito Akihiko
  • Journal Title: Journal of Diabetes and its Complications Volume: 36 Issue: 11 Pages: 108312-108312
  • DOI: 10.1016/j.jdiacomp.2022.108312
  • Peer Reviewed / Open Access
• [Presentation] Two forms of urinary megalin excretion are novel predictors of the progression of early-stage diabetic kidney disease in type 2 diabetes (2018)
  • Author(s): Tomomichi Iida, Michihiro Hosojima, et al.
  • Organizer: ISN Frontiers Meetings
  • Int'l Joint Research
• [Presentation] 早期の糖尿病腎症における腎予後予測マーカーとしての尿中メガリン測定の意義 (2017)
  • Author(s): 飯田倫理，細島康宏ら
  • Organizer: 第60回日本糖尿病学会年次学術集会