| Project/Area Number |
22K08083
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Osaka Metropolitan University |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Completed (Fiscal Year 2024)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2024: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Liver firbosis / Cytoglobin / Hemoglobin / Neuroglobin / Antioxidants / Anti-fibrosis / ROS / Globin / Myoglobin / Antioxidant |
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| Outline of Research at the Start |
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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| Outline of Final Research Achievements |
We characterized the biological activities of globins in cultured human HSCs (HHSteCs) and their effects on carbon tetrachloride (CCl4)-induced cirrhosis in mice. All globins demonstrated greater antioxidant capacity than glutathione in cell-free systems. MB, NGB, and CYGB, but not HB, scavenged reactive oxygen species generated spontaneously or stimulated by H2O2 or transforming growth factor β1 in HHSteCs and reduced collagen 1A1 production via suppressing COL1A1 promoter activity. RNA sequencing of MB- and NGB-treated HHSteCs revealed downregulation of extracellular matrix;encoding and fibrosis-related genes and HSC deactivation markers. Importantly, administration of MB, NGB, and CYGB suppressed CCl4-induced mouse liver fibrosis. These findings revealed unexpected roles for MB and NGB in deactivating HSCs and inhibiting liver fibrosis development, suggesting that globin therapy may represent a new strategy for combating fibrotic liver disease.
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| Academic Significance and Societal Importance of the Research Achievements |
Our study revealed new applications for exogenous globin administration to treat liver fibrosis. MB and NGB as well as CYGB inhibited COL1A1 production by activated HSCs and prevented liver inflammation and liver fibrosis via intracellular ROS-scavenging functions.
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