Detection of DNA damage response in nonalcoholic fatty liver disease via p53-binding protein 1 nuclear expression.

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09362
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagasaki University
• Principal Investigator: AKAZAWA Yuko 長崎大学, 原爆後障害医療研究所, 准教授 (80582113)
• Co-Investigator(Kenkyū-buntansha): 中尾 一彦 長崎大学, 医歯薬学総合研究科(医学系), 教授 (00264218) ; 中島 正洋 長崎大学, 原爆後障害医療研究所, 教授 (50284683)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 非アルコール性脂肪肝炎 / NAFLD / DNA損傷応答 / 53BP1 / 発癌

Outline of Final Research Achievements

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. However, the pathogenesis of hepatocellular carcinoma in NAFLD is largely unexplored. p53-binding protein 1 (53BP1), a DNA damage response molecule, accumulates at DNA double-strand break regions, forms a nuclear focus, and serves as a molecular marker of genomic instability during carcinogenesis in various malignancies. Therefore, the aim of this study was to evaluate the significance of 53BP1 expression in hepatocytes of human NAFLD. In the human liver biopsy tissues, abnormal 53-BP1 nuclear foci in hepatocytes were significantly elevated NAFLD livers, compared to normal controls (p < 0.01). Large 53BP1 foci were positively associated with pathological fibrotic score and age of patients, and negatively associated with platelet counts. These results suggest that DNA damage in hepatocytes form large 53BP1 foci in patients with NAFLD, potentially contributing to carcinogenesis.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

NAFLDにおける肝細胞における53BP1核内フォーカス発現解析は、独特の“ゲノム不安定性”病態マーカーとして確立できる可能性がある。ヒトNAFLD肝における53BP1発現と発癌のリスクの関係が評価できれば、当手法は安価で簡便であるためNASHにおける発癌予測の指標となり、臨床診断学への応用が期待できる。