Investigating compounds that act on interglomerular crosstalk in diabetic nephropathy.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08729
• 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: Kumamoto University
• Principal Investigator: Mizumoto Teruhiko 熊本大学, 大学院生命科学研究部(医), 助教 (80749193)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 糖尿病性腎症 / エクソソーム

Outline of Final Research Achievements

We focused on Compound X, an HSP-90 inhibitor screened from the drug library, and administered it to streptozocin (STZ) rats, a model of diabetic nephropathy, to examine its efficacy in inhibiting the progression of nephropathy. The results showed that Compound X predominantly inhibited the progression of nephropathy in STZ rats. However, the inhibition of exosome uptake by HSP90 inhibitors could not be fully verified. Therefore, we investigated HSP-90 in renal glomerular cells using the cRNA-seq database and found that HSP-90 is strongly expressed in glomerular component cells such as mesangial cells. This suggested that HSP90 inhibitors may also act directly on renal glomeruli.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎症による腎症進展は治療薬がレニン・アンジオテンシン系阻害薬、最近有効性が明らかになったSGLT2阻害薬などに限定されている。本研究のエクソソーム阻害による新たな機序は病態的意義を検討した報告は腎領域でも散見されるが、本機序をターゲットとした治療については報告が認められていない。既存薬ライブラリーから選出した化合物Xは糖尿病性腎症ラットの腎症進展を抑制していたため、新しい機序の糖尿病性腎症の治療薬へ繋がる可能性がある。