Characterization of regulatory expression of bovine hepcidin, a hormone responsible for iron homeostasis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06365
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42010:Animal production science-related
• Research Institution: Kyoto University
• Principal Investigator: Funaba Masayuki 京都大学, 農学研究科, 教授 (40238655)
• Co-Investigator(Kenkyū-buntansha): 松井 徹 京都大学, 農学研究科, 名誉教授 (40181680)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 畜産学 / 栄養学 / シグナル伝達

Outline of Final Research Achievements

Hepcidin is a liver-derived hormone responsible for iron homeostasis. The present study characterized regulatory expression of bovine hepcidin in animal studies as well as cell culture studies. Anemia in newborn calves was improved by iron supplementation, but plasma hepcidin levels were not changed by iron supplementation. Plasma iron levels in fattening cattle were elevated by vitamin A restriction, but hepatic hepcidin expression was unaffected. Activity of bovine Smad4 to mediate hepcidin transcription was weaker than that of murine Smad4 due to lower stability of bovine Smad4 mRNA and consequently low Smad4 protein levels. PPARs promoted bovine hepcidin transcription, and MITF/TFE promoted mouse hepcidin transcription.

Free Research Field

家畜栄養学

Academic Significance and Societal Importance of the Research Achievements

鉄恒常性は健康維持上重要である。ヘプシジン発現制御を通して鉄恒常性は維持される-鉄栄養の変化に応じてヘプシジン発現の増減は起こる-ことがマウスやヒトでの知見から明らかにされている。本研究において、ウシヘプシジン発現は鉄栄養状態の変化に鋭敏には応答しないこと、その理由の一つとして、ヘプシジン転写を促進するSmad4の発現制御がウシで特徴的であること、ウシヘプシジン転写を促進する新規の因子を明らかにした。本研究結果は、マウスやヒトでの知見は必ずしもそのままウシに適用できないことを明示している。