Disecting the effect of glucoraphanin, an Nrf2 activator, on diabetic nephropathy.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17271
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: Bessho Ryoichi 旭川医科大学, 大学病院, 医員 (10869358)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Glucoraphanin / 糖尿病性腎症 / Nrf2 / SGLT2

Outline of Final Research Achievements

NF-E2-related Factor 2 (Nrf2) activators have renoprotective potential, however their mechanisms are not fully elucidated. In this study, we investigated the effect of Glucoraphanin (GR), an Nrf2 activator derived from broccoli sprouts, and its active form, sulforaphane (SFN), on diabetic nephropathy.
We treated wild-type and Nrf2-deficient (C57BL/6J background) mice, made diabetic by a high-fat diet and low-dose streptozotocin, with a GR containing diet. GR did not affect glomerular lesions and albuminuria, but improved tubular damage and renal fibrosis in both wild-type and Nrf2-deficient diabetic mice.
GR decreased Sodium-Glucose co-Transporter 2 (SGLT2) protein expression in wild-type and Nrf2-deficient diabetic mice. In addition, SFN showed an Nrf2-independent decrease in SGLT2 gene expression in cultured human proximal tubular epithelial cells. These results suggest that GR may have renoprotective effects in a Nrf2-independent manner, and the involvement of SGLT2 down-regulation.

Free Research Field

糖尿病性腎症

Academic Significance and Societal Importance of the Research Achievements

本研究では、ブロッコリー新芽由来生理活性物質Glucoraphanin(GR)の腎保護効果とその作用機構の一端を明らかにした。従来、GRの腎保護作用機構には、レドックス制御因子NF-E2-related Factor 2 (Nrf2)活性化の影響が大きいと考えられていた。しかし本検討により、GRのNrf2非依存的な腎保護効果が明らかとなり、Sodium-Glucose co-Transporter 2 (SGLT2)発現減少の関与が示唆された。本研究成果は、積極的・特異的治療法の乏しい糖尿病性腎症に対する新規創薬への応用や、新規治療標的の発見への展開が期待できる。