Elucidation of phenotypic determinants in pediatric primary focal glomerulosclerosis by RNA-seq analysis

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K10138
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyorin University (2018-2022); Tokyo Medical and Dental University (2017)
• Principal Investigator: Tanaka Eriko 杏林大学, 医学部, 講師 (80439827)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: ネフローゼ症候群 / RNA sequencing / 腎糸球体 / 細胞分化 / 免疫分子

Outline of Final Research Achievements

We performed RNA sequencing to analyze RNA expressions in the glomerulus of pediatric nephrotic syndrome patients. Nine samples (7 minor glomerular abnormalities, and 2 focal segmental nephrotic syndrome) were analyzed. We found that RNA expressions concerning cell motility and cellular differentiation significantly changed. There were no differences between disease types. Comparing the result of RNA sequencing of whole kidney specimens from five samples revealed that the whole kidney showed significant changes in RNA expressions concerning immunity, whereas the glomerulus showed no changes in RNA expressions of immunity. Taken together, we speculated that the immunity alternation in the kidney affects the cell functions in the glomerulus, leading to development of nephrotic syndrome.

Free Research Field

小児腎臓病学

Academic Significance and Societal Importance of the Research Achievements

小児ネフローゼ症候群は、免疫異常を背景に腎糸球体のポドサイトの形態変化をきたし発症することが言われているが、その発症機序の詳細は未だに解明されていない部分が多い。また、これまでに実際の腎組織における遺伝子発現の変化を包括的に解析した研究はほとんどない。本研究では小児ネフローゼ症候群患者の腎糸球体におけるRNA発現を解析することで、尿蛋白漏出の直接的な原因となる遺伝子発現の変化を確認することができた。この研究により小児ネフローゼ症候群の病態機序解明に近づき、病態に基づいた治療の開発に繋げることができると期待される。