2005 Fiscal Year Final Research Report Summary
Roles of non-coding H19 mRNA in hepatocyte proliferation and differentiation
| Project/Area Number |
16590303
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Akita University |
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Principal Investigator |
NISHIKAWA Yuji Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (90208166)
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| Co-Investigator(Kenkyū-buntansha) |
OMORI Yasufumi Akita University, School of Medicine, Assistant Professor, 医学部, 講師 (90323138)
YOSHIOKA Toshiaki Akita University, School of Medicine, Research Associate, 医学部, 助手 (80302264)
ENOMOTO Katsuhiko Akita University, School of Medicine, Professor, 医学部, 教授 (20151988)
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| Project Period (FY) |
2004 – 2005
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| Keywords | H19 / Non-coding RNA / Hepatocytes / Proliferation / Differentiation / Liver injury / Liver regeneration |
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| Research Abstract |
(1)Increased H19 gene expression in various liver injury models
i)H19 gene expression was markedly increased in the rat liver after administration of carbon tetrachloride. The peak of expression was 4 days after the treatment, while hepatocyte proliferation was peaked after 3 days. By performing BrdU immunohistochemistry and H19 in situ hybridization on the same tissue sections, it was suggested that H19 gene expression took place in the hepatocytes which underwent DNA synthesis. ii)In the cirrhotic livers induced by repeated carbon tetrachloride administrations, H19 gene expression was chronically elevated. Dimethylnitrosamine-induced chronic liver injury also increased the gene expression. Furthermore, strong H19 gene expression was observed in the livers of LEC (a Wilson disease model) and bile duct-ligated rats. These results suggested that H19 gene expression might be a useful indicator of liver injury or remodeling.
(2)Possible roles of H19 gene in hepatocyte proliferation and differentiation
i)We constructed an H19 gene expression vector (pc3GF-H19) and introduced it into primary rat hepatocytes isolated from the rat by the lipofection method. There were no morphological or proliferative changes in the H19-overexpressing hepatocytes. ii)The livers of the H19 knockout mice (provided by Dr. Tilghman [Princeton University, U.S.A.]) showed normal architecture, although the nuclei of hepatocytes appeared to be larger as compared with the control mice (C57BL). Preliminary experiments demonstrated that, after a two-thirds partial hepatectomy, the knockout mouse livers regenerated normally. iii)Expression of proliferating nuclear antigen was normal in hepatocytes isolated from the H19 knockout mice and cultured in the presence of EGF. iv)Hepatocytes from H19 knockout mice demonstrated dendritic morphogenesis within the collagen gel matrix, which was similar to that by hepatocytes from the control mice.
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