2003 Fiscal Year Final Research Report Summary
Hepatocyte growth factor accelerates proliferation and differentiation of hepatic oval cells in a 2-acetylaminofluorene/partial hepatectomy model in rat
| Project/Area Number |
14370186
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | 宮崎医科大学 |
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Principal Investigator |
TSUBOUCHI Hirohito Miyazaki Medical College, University of Miyazaki, Department of Internal Medicine II, Professor, 医学部, 教授 (60145480)
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| Co-Investigator(Kenkyū-buntansha) |
IDO Akio Kyoto University Hospital, Department of Experimental Therapeutics, Translational Research Center, Associate professor, 大学院・医学研究科, 助教授 (30291545)
UTO Hirofumi Miyazaki Medical College, University of Miyazaki, Department of Internal Medicine II, Assistant Professor, 医学部, 助手 (20347058)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Hepatocyte Growth Factor (HGF) / hepatic stem cell / oval cell / 70% partial hepatectomy / 2-acethylaminofluorene / antibody array / c-kit / AFP |
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| Research Abstract |
Hepatocyte growth factor (HGF) is known as a major agent promoting the proliferation of mature hepatocytes. Several investigators have recently shown that HGF is an important factor in differentiation and proliferation of hepatic progenitor cells, and in the differentiation of embryonic stem cells into hepatocytes. But it is unclear whether HGF could accelerate the differentiation of these cells in vivo. In this study, we investigated the effect of HGF on proliferation and differentiation of hepatic oval cells, one of hepatic stem cell candidates, using a 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH) model in rat. The proliferation of oval cells in rat livers in a 2-AAF/PH model was stimulated by intraperitoneal administration of recombinant human HGF (rhHGF). Periportal basophiic areas consisting of oval cells and proliferating cell nuclear antigen-positive cells in oval cell clusters in rat livers treated with rhHGF were significantly increased in comparison with oval cell clusters without rhHGF on day 8. The expression of c-Kit and α-fetoprotein on oval cell with rhHGF were higher than control at day 4 and lower at day 12. The pattern of CK 19 expression was the same in both groups in all phases. Furthermore, administration of rhHGF stimulated mRNA expression of albumin, hepatocyte nuclear factor-1 α and -4α on Day 4. It is suggested that treatment with rhHGF induced proliferation and differentiation of oval cells through up-regulation of hepatocyte nuclear factor-1 α and -4α in liver tissue of 2-AAF/PHx model rats. These results indicate that rhHGF promotes differentiation and proliferation of hepatic progenitor cells, and the administration of rhHGF could become a new treatment modality inducing liver regeneration in patients with liver failure.
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