研究課題/領域番号 |
22K08083
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研究種目 |
基盤研究(C)
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配分区分 | 基金 |
応募区分 | 一般 |
審査区分 |
小区分53010:消化器内科学関連
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研究機関 | 大阪公立大学 |
研究代表者 |
LE THITHANHTHUY 大阪公立大学, 大学院医学研究科, 特任講師 (10572175)
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研究期間 (年度) |
2022-04-01 – 2025-03-31
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研究課題ステータス |
交付 (2022年度)
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配分額 *注記 |
4,290千円 (直接経費: 3,300千円、間接経費: 990千円)
2024年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2023年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2022年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
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キーワード | Globin / Cytoglobin / Neuroglobin / Myoglobin / Hemoglobin / Antioxidant / Anti-fibrosis |
研究開始時の研究の概要 |
These scientific originality of the anti-fibrotic capacity of rhCYGB protein suggests an investigation whether other members of globin family such as hemoglobin (HB), myoglobin (MB), and neuroglobin (NGB) possess the similar effect. We investigated the role of these proteins in liver fibrosis.
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研究実績の概要 |
We have explored that other heme-binding proteins such as hemoglobin (HB), myoglobin (MB), and neuroglobin (NGB) which also possing the gas binding, and ROS scavenging function, have showed the same anti-fibrotic properties as CYGB. The antioxidant, and ROS scavenging function of human HB, MB, and NGB in comparison with CYGB as well as structure alteration regulating their function have been examined. Intra-cellular and tissue bio-distribution, the kinetics, safety assay, and anti-fibrotic function of these globins were demonstrated both in vitro and in vivo.
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現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
We performed RNA-seq analysis in rhNGB and MB-treated HHSteCs compared with untreated controls. We investigated the common and differential pathways activated in HHSteCs treated with 4 μM MB or NGB (n = 3, each group). The RNA-seq data revealed that 2977 and 1637 genes were significantly changed by 2-fold or greater in the MB and NGB treatment groups, respectively, compared with untreated controls. RNA-seq analysis revealed the downregulation of ECM-encoding and fibrosis-related genes, and the upregulation of transcription factors that regulate the deactivation phenotype of HHSteCs, including PPARγ, ETS1, ETS2, and Interferon regulatory factor (IRF) 1. These findings were confirmed by quantitative reverse transcriptase-polymerase chain reaction.
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今後の研究の推進方策 |
Determine the specific and common mechanism action of these globins related to their anti-fibrotic activity. We need to explore the common and specific pathways related to anti-inflammation, and anti-fibrosis function of these globins via heatmap analysis, and enrichment analysis, a comprehensive resource for curated gene sets and a search engine that accumulates biological knowledge for further biological discoveries (Enrichr is freely available at: http://amp.pharm.mssm.edu/Enrichr.). Examining the potential specific targets which binding to these globins may induce conformation changes and facilitate their function. Taken together, these data will shed new light on the function and application of CYGB, MB, and NGB in liver diseases.
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