Elucidation of molecular pathogenesis of interstitial cystitis based on microRNA expression signature

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16779
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Dokkyo Medical University
• Principal Investigator: Fuse Miki 獨協医科大学, 医学部, 講師 (90568627)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 間質性膀胱炎 / マイクロRNA / miR-320 / 転写因子 / E2F-1 / E2F-2 / TUB

Outline of Final Research Achievements

We created the microRNA (miRNA) expression signature by using interstitial cystitis (IC) clinical specimens. Analysis of our signature revealed that a total of 366 miRNAs (203 downregulated and 163 upregulated) were aberrantly expressed in IC tissues. In particular, miR-320 family miRNAs (miR-320a, miR-320b, miR-320c, miR-320d and miR-320e) had downregulated expression in IC tissues. Genome-wide gene expression analyses and in silico database analyses showed that three transcription factors, E2F-1, E2F-2 and TUB, are regulated by miR-320 family miRNAs. Immunostaining of IC tissues confirmed that these transcription factors are overexpressed in IC tissues.

Free Research Field

排尿機能

Academic Significance and Societal Importance of the Research Achievements

間質性膀胱炎は、原因不明の難治性膀胱炎であり、頻尿や痛みといった症状により患者のQOLを著しく低下させるが、いまだ客観的な診断法や有効な治療法がない難治性疾患である。本研究では、間質性膀胱炎の病態解明に向けて臨床検体におけるマイクロRNA発現プロファイルの作成し、間質性膀胱炎に関わる分子ネットワークの探索を行った。その結果、3つの転写因子（E2F-1, E2F-2, TUB）が間質性膀胱炎臨床検体において高発現している事を明らかにした。マイクロRNAを起点とした解析により、本疾患の分子病理学的理解が進む事が期待できる。