Deciphering iron efflux mechanism by exosomes in hepatocytes

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19720
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Nippon Medical School
• Principal Investigator: Sakai Mashito 日本医科大学, 大学院医学研究科, 大学院教授 (40643490)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 鉄代謝 / 肝細胞 / エクソソーム

Outline of Final Research Achievements

Iron is an essential metal for cell survival; however, excess iron increases the production of reactive oxygen species and causes tissue damage. The liver plays a central role in maintaining systemic iron homeostasis, while serving as the primary site of iron storage.
In this study, we carried out a proteomic analysis of exosomes in the livers of iron-loaded mice. Additionally, we investigated the therapeutic implications of iron export from hepatocytes in the iron-loaded model.

Free Research Field

病態生化学

Academic Significance and Societal Importance of the Research Achievements

原発性鉄過剰症である遺伝性ヘモクロマトーシスは、コーカソイドでは頻度の高い疾患であり、肝硬変、糖尿病、心筋症などの原因となる。一方、わが国では、鉄代謝関連分子の変異に起因しない続発性鉄過剰症が主体だが、最も頻度の高い輸血後鉄過剰症では、同様の全身性の病態を呈する。本研究では、新しい治療原理に基づく鉄過剰症治療の開発を目的として、肝細胞のエクソソーム依存性鉄排出の治療応用を検討した。