Elucidation of the role of the ubiquitin ligase KLHL3 in the pathogenesis of diabetic kidney disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17719
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Teikyo University
• Principal Investigator: Ishizawa Kenichi 帝京大学, 医学部, 講師 (10772684)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: KLHL3 / リン酸化

Outline of Final Research Achievements

In this study, we focused on the phosphorylation of the ubiquitin ligase component Kelch-like 3 (KLHL3), a novel effector of angiotensin II, and analyzed its relationship with diabetic kidney disease. In addition to the distal tubules of diabetic model mice (db/db), KLHL3-Ser433 phosphorylation signals are also observed in the thick ascending limb (TAL) of Henle's loop, and the expression of NKCC2 expressed at the same site is also upregulated. We also investigated the existence of phosphorylated KLHL3 in humans and detected phosphorylated KLHL3 in human renal biopsy specimens and urine exosome fractions.

Free Research Field

腎臓病学

Academic Significance and Societal Importance of the Research Achievements

本研究では、糖尿病性腎臓病におけるKLHL3リン酸化の病的役割について検討し、病態の一端を解明した。また、ヒトにおいて腎臓と尿exosome分画でKLHL3リン酸化を検出したため、今後の臨床応用が期待できる。