Role of iron in the tisue repair response after liver injury

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15396
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Kumamoto University
• Principal Investigator: Kanamori Yohei 熊本大学, 大学院生命科学研究部(医), 助教 (70838903)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 鉄代謝 / 肝臓 / 組織修復

Outline of Final Research Achievements

This study explored the role of iron valent status in the progression of hepatitis. Liver fibrosis was ameliorated in liver-specific FBXL5 knockout mice, which exhibit ferrous iron accumulation in the liver, subjected to liver injury. In contrast, liver fibrosis was comparable between wild-type and FBXL5, IRP2 double knockout mice, which exhibit ferric iron accumulation in the liver. These results suggest that ferrous iron specifically exerts antifibrotic roles in liver injury. Hepatic mRNA levels of collagens and the numbers of activated fibroblasts were similar between wild-type and FBXL5 knockout mice. On the other hands, higher expression of matrix metalloproteinases was observed in the livers of FBXL5 knockout mice compared with those of wild-type mice. These results suggest that hepatocyte ferrous iron promotes degradation of collagens, thereby suppressing liver fibrosis progression.

Free Research Field

鉄代謝

Academic Significance and Societal Importance of the Research Achievements

肝疾患と鉄代謝異常の関連性が古くから提唱されているものの、鉄が肝疾患の進展に果たす意義に関する共通見解は得られていない。鉄は生体内において2価と3価の状態を変化させることにより、生物学的に異なる機能を発揮するため、2価鉄の蓄積と3価鉄の蓄積とでは全く違う状況と言える。しかし、2価鉄／3価鉄の価数動態と肝疾患の進展との関係はほとんど明らかにされていない。鉄の総量に注目した過去の研究とは視点の異なる本研究は、肝疾患における鉄の意義に関する議論に新たな展開をもたらすと期待される。