| Project/Area Number |
23K24322
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| Project/Area Number (Other) |
22H03061 (2022-2023)
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Multi-year Fund (2024)
Single-year Grants (2022-2023) |
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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 |
Kawada Norifumi 大阪公立大学, 大学院医学研究科, 教授 (30271191)
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| Co-Investigator(Kenkyū-buntansha) |
松原 三佐子 (佐藤三佐子) 大阪公立大学, 大学院獣医学研究科, 准教授 (00635120)
LE THITHANHTHUY 大阪公立大学, 大学院医学研究科, 准教授 (10572175)
Hoang Hai (HOANG HAI) 大阪公立大学, 大学院医学研究科, 特任講師 (60623246)
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| Project Period (FY) |
2024-04-01 – 2025-03-31
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| Project Status |
Completed (Fiscal Year 2024)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2024: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
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| Keywords | 肝細胞癌 / 肝星細胞 / サイトグロビン / CD40 / 腫瘍免疫 / 星細胞 / 肝線維化 / Cytoglobin / コラーゲン / TGFβ / ROS / TGF-β |
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| Outline of Research at the Start |
継続課題のため、記入しない
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| Outline of Final Research Achievements |
This study elucidated the roles of HSC-derived CYGB and CD40 in HCC pathogenesis.NGS revealed that 33 CpG sites in the CYGB promoter region were highly methylated in HCC tissues compared to adjacent non-tumor tissues.Overexpression of CYGB in Huh7 cells suppressed proliferation and migration. CD40 expression was elevated in poorly differentiated HCCs compared to well-differentiated HCCs and HSCs.Methylation analysis of the CD40 promoter showed hypomethylation in poorly differentiated HCC and HSCs, contrasting with hypermethylation in HepG2 and Huh7.Co-culture experiments demonstrated that CD40–CD40L interactions, involving activated CD4⁺ T cells, increased apoptosis in HLF cells compared to controls. CD40 neutralization enhanced apoptosis,while integrin α5β1 neutralization suppressed it,suggesting CD40–CD40L interactions protect HCC cells from apoptosis. These findings highlight the critical interplay between HSCs,HCC cells,and immune cells in liver carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、CYGBとCD40が肝発がんに関与する新たな分子機構を解明し、HSC-肝細胞-免疫細胞のクロストークの重要性を示した。学術的には、組織線維化と腫瘍免疫の相関解明に貢献し、グロビン研究に新視点を提供した。臨床医学的には、肝がんの早期診断や新規治療法開発につながる可能性があり、高リスク群の予後改善に寄与する。
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