The role of PDCD4 and microRNA in glomeruli in the development of chronic kidney disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K16951
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: The University of Tokushima
• Principal Investigator: SHIBATA Eriko 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (40831516)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: PDCD4 / 慢性腎炎

Outline of Final Research Achievements

We focused on the role of the cell cycle control protein PDCD4 (Programmed Cell Death 4) in chronic nephritis. In situations where cell proliferation is promoted, rpS6 (ribosomal protein S6) phosphorylation increases and PDCD4 expression decreases. In human IgA nephropathy kidney tissue, PDCD4 and phosphorylated rpS6 were stained mainly in mesangial cells. In the rat Thy1 nephritis model, phosphorylated rpS6 expression was strong on the 7th day after Thy1 administration, whereas PDCD4 expression peaked on the 3rd day and attenuated on the 7th day. When steroid therapy was administered from the time of Thy1 administration, PDCD4 expression was maintained even on day 7, and rpS6 expression decreased.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病は日本人の1330万人程度と考えられている。慢性腎炎はわが国における新規透析導入原因疾患の第3位であり，その割合は次第に減少しているが根絶できておらず，残余リスクに対するアプローチが課題である。PDCD4の発現は一様でなく解釈が困難であるが，細胞増殖の初期に発現し，特に細胞増殖が強い場合に発現量が増える可能性が示唆された。PDCD4は細胞増殖を負に制御すると考えられているので，PDCD4の発現量を調節することができれば，メサンギウム増殖を伴う腎疾患における新規治療法を見出すことができる可能性が示唆された。