Exploration of the cell population that repairs damaged proximal tubules

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17707
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Kyoto University
• Principal Investigator: Kitai Yuichiro 京都大学, 医学研究科, 医員 (90839771)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腎修復 / 近管尿細管 / 障害度 / 幹細胞

Outline of Final Research Achievements

Injured proximal tubules (PT) are restored by the proliferation of PT cells, but the influence of injury severity is uncertain. First, we showed highly proliferative capacity of superficial PT cells, after severe ischemia than in moderate ischemia. Recently, A Runx1 enhancer, Runx1+24mCNE (eR1) was identified as a marker of adult hematopoietic and gastric stem cells. We traced eR1-activated PT cells, using mice that can visualize eR1 activity. In uninjured kidneys and moderately injured kidneys, eR1-activated PT cells were almost absent. However, many PT cells with clonal expansion showed high eR1 activity only after severely injured kidneys. RNA-seq data showed a highly proliferative capacity of eR1-activated PT cells. In severe injury, clonal expansion of eR1-activated proximal tubular cells contributes to the regeneration of superficial proximal tubules.

Free Research Field

腎臓病学

Academic Significance and Societal Importance of the Research Achievements

近位尿細管は腎臓全体の約6割を占め、急性腎障害の際に強く障害される。近位尿細管障害後、近位尿細管は近位尿細管細胞の増殖によって修復されることが知られているが、修復の主体となる細胞群は明らかにされていない。障害時に優先的に修復に関わる細胞群が同定できれば、腎臓の再生修復の分野の発展に寄与できる可能性がある。当研究で得られた、重度障害でのみ強く増殖する一群がいるという結果は、新しい視点から尿細管修復機構を追究できる可能性を示唆している。