The effects of a candidate compound for hematopoiesis of that induces ectopic EPO gene expression via GATA inhibition.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19KK0398
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Tohoku University
• Principal Investigator: HIRANO IKUO 東北大学, 医学系研究科, 講師 (00708117)
• Project Period (FY): 2020 – 2023
• Keywords: GATA1 / GATA2 / Erythropoietin / GATA inhibitor / Doping

Outline of Final Research Achievements

Erythropoietin (EPO) is a cytokine produced in the kidney and induces erythropoiesis. Recently, inhibitors of GATA transcription factors have been reported as agents capable of inducing ectopic expression of the Epo gene in the lungs and other organs. In this study, we analyzed the effects of systemic GATA inhibition on the hematopoietic system and the mechanism of Epo gene regulation by GATA factors in vivo by using genetically engineered mice. The results showed that systemic GATA factor inhibition causes severe hematopoietic defects and that GATA factors may be rather positively involved in the regulation of renal Epo gene expression.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、成体の造血系における転写因子GATA1、GATA2の機能を明らかにするうえで重要な知見となるものである。GATA阻害剤によるEpo遺伝子発現誘導効果は、新規貧血改善薬の開発につながると期待されるが、今回の解析結果はGATA阻害による造血系への抑制性作用、および主要なEPO産生細胞でのEPO産生制御へのGATA因子の正の関与を示すものであり、GATA阻害によるEPO産生誘導効果を得るには組織特異性を高める必要があることを示せたと考える。また、本研究の結果はドーピングなどでのGATA阻害剤の安易な使用を抑制する意味でも社会的意義があったと考えている。