FRET imaging of regulated necrosis in mouse sepsis model

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K05238
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 27040:Biofunction and bioprocess engineering-related
• Research Institution: Toho University
• Principal Investigator: Murai Shin 東邦大学, 医学部, 助教 (90287540)
• Co-Investigator(Kenkyū-buntansha): 中野 裕康 東邦大学, 医学部, 教授 (70276476)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ネクロプトーシス / FRETイメージング / RIPK3 / 敗血症 / 急性腎疾患

Outline of Final Research Achievements

We generated transgenic mice systemically expressing a FRET biosensor that can monitor the induction of regulated necrosis (RN) in living cells in order to determine where and when RN is induced in the pathological tissue. As a result of in vivo FRET imaging in mouse models for human diseases using the transgenic mouse, the new findings were obtained regarding the mechanism by which RN exacerbates the pathological condition as followed.
1) RN was induced in jejunal crypt epithelial cells in a mouse sepsis model by excess TNF, suggesting that this causes tissue damage with loss of intestinal epithelial cells.
2) In an acute kidney injury model, from the results that RN was induced in renal tubular epithelial cells after the proximal tubular occlusion by cisplatin administration, it was suggested that the cause of renal tubular damage was the induction of RN in renal tubular epithelial cells triggered by tubular occlusion.

Free Research Field

病態医化学

Academic Significance and Societal Importance of the Research Achievements

本研究では虚血性疾患や炎症性疾患において計画的ネクローシス（RN）誘導による病態増悪のメカニズムを継時的に解析するためのトランスジェニックマウスを作製した。マウス病態モデルにおいてRN誘導部位の特定と組織障害までを継時的にモニターすることに国内外を通じて初めて成功した。作製したトランスジェニックマウスはバイオリソースとして高い独自性を有しており、さまざまな病態モデルに利用することで疾患の原因となるRNを時空間的に解析するという新規性の高い研究を創造できる。