Development of therapy for hemolytic uremic syndrome with a focus on microRNA/high mobility group box-1 signaling

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17748
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Ryo Maeda 福島県立医科大学, 医学部, 助教 (60792025)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 溶血性尿毒症症候群 / HMGB1 / miRNA

Outline of Final Research Achievements

Typical (Shiga toxin-producing Escherichia coli-associated) hemolytic uremic syndrome (HUS) is the leading cause of acute kidney injury in children, and no specific treatment methods have been established. In HUS-model mice treated with Shiga toxin 2 (Stx2) and lipopolysaccharide (LPS), we conducted array analyses to identify changes in the expression of target microRNAs involved in high mobility group box-1 signaling. We focused on dual Specificity Phosphatase 8 (DUSP8), a miR-21-related mRNA with a large magnitude fold-change. DUSP8 expression was higher in the kidneys of HUS-model mice than in the kidneys of healthy mice. Proximal convoluted tubule (TKPTS) and collecting duct cells (M-1) treated with Stx2 and LPS in vitro showed no appreciable changes. A possible reason is the use of immortalized cells. Thus, we will use primary mouse renal tubular cells in reexaminations.

Free Research Field

腎臓病学

Academic Significance and Societal Importance of the Research Achievements

HUSモデルマウスとmiRNAとの関与を検討した報告は少ない。本研究ではmiRNAのmiR-21に関連するmRNAのDUSP8がHUSの病態に関与している可能性が示唆された。さらなる検証を進めることでHUSとmiR-21やDUSP8との関連を明らかにでき、病態が解明されることで未だ特異的治療法のないHUSの治療法が確立しうるため、本研究の学術的意義は高い。