Development of a method for differentiating various renal disorders by analyzing podocyte activation signals

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07367
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: The University of Tokushima
• Principal Investigator: SAKURAI Akiko 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (70707900)
• Co-Investigator(Kenkyū-buntansha): 冨永 辰也 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (80425446) ; 田蒔 昌憲 徳島大学, 病院, 講師 (90528902)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ポドサイト / バイオマーカー

Outline of Final Research Achievements

Analyzed CXCR-4 and CXCR-7, which are present in the cell membrane of podocytes and are the direct cause of proteinuria and decline in renal function. Using cultured immortalized human podocytes, changes in CXCR-4 and CXCR-7 gene expression levels under hyperglycemic stimulation, hydrogen peroxide stimulation, BMP4 stimulation, and SDF-1 stimulation were confirmed by Real-Time PCR. In addition, confirm the expression of CXCR-4 and CXCR-7 proteins in exosomes excreted in human urine, we investigated a method for extracting urinary exosomes using occasional urine from healthy subjects and urine samples from patients. Elucidate the functions of podocyte-specific molecular groups that reflect pathological conditions in a diabetic nephropathy model, changes in the expression of CXCR-4 and CXCR-7 were analyzed using immunohistochemical staining in mouse kidney tissues collected over time.

Free Research Field

内科学一般

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病(CKD)の主たる原因である糖尿病性腎症によって新規に透析導入となる患者数は最も多い。現行の治療法では、腎不全への進展をわずかに遅延させるのみであり、他のCKDの原因と比較しても、予後は極めて不良である。そのため、診断法を明確なものとし、腎症に特異性の高く、有効な治療法を開発することは急務である。腎症における分子病態を統合的に理解し、腎症の病態・病期ごとに特異的な分子を抽出し、ポドサイトの活性化シグナルの解析による各種腎障害の鑑別法の探索を行うことで、腎臓病の分子病態把握、治療の奏功性の評価、透析にいたる予後予測等の評価ができると考える。