Hepatocyte growth factor accelerates proliferation and differentiation of hepatic oval cells in a 2-acetylaminofluorene/partial hepatectomy model in rat

肝细胞生长因子加速大鼠 2-乙酰氨基芴/部分肝切除模型中肝卵圆细胞的增殖和分化

基本信息

  • 批准号:
    14370186
  • 负责人:
  • 金额:
    $ 9.02万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    2002
  • 资助国家:
    日本
  • 起止时间:
    2002 至 2003
  • 项目状态:
    已结题

项目摘要

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.
肝细胞生长因子(HGF)是促进成熟肝细胞增殖的主要因子。最近几个研究者已经表明,HGF是肝祖细胞分化和增殖以及胚胎干细胞分化为肝细胞的重要因素。但目前尚不清楚HGF是否能促进这些细胞在体内的分化。本研究采用2-乙酰氨基芴/部分肝切除(2-AAF/PH)大鼠模型,观察HGF对肝卵圆细胞增殖和分化的影响。在2-AAF/PH模型中,腹腔注射重组人肝细胞生长因子(rhHGF)刺激大鼠肝卵圆细胞增殖。门静脉周围嗜碱性区域组成的卵圆细胞和增殖细胞核抗原阳性细胞在卵圆细胞簇在大鼠肝脏与rhHGF处理相比,没有rhHGF的卵圆细胞簇在第8天显着增加。与对照组相比,rhHGF组卵圆细胞c-Kit和甲胎蛋白的表达在第4天升高,第12天降低。CK 19的表达模式在两组中的所有时相都是相同的。此外,给予rhHGF刺激第4天白蛋白、肝细胞核因子-1 α和-4α的mRNA表达。rhHGF可能通过上调2-AAF/PHx模型大鼠肝组织中肝细胞核因子-1 α和-4α的表达,促进卵圆细胞的增殖和分化。这些结果表明,rhHGF促进肝祖细胞的分化和增殖,rhHGF的管理可能成为一个新的治疗模式诱导肝再生的肝衰竭患者。

项目成果

期刊论文数量(34)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
井戸章雄, 他: "HGFを用いた肝再生療法"最新医学. 58・9. 2023-2029 (2003)
Akio Ido 等:“使用 HGF 的肝脏再生治疗”最新医学 58・9 2023-2029(2003)。
  • DOI:
  • 发表时间:
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  • 影响因子:
    0
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  • 通讯作者:
Onaga M, et al.: "Enhanced expression of growth factors and imbalance between hepatocyte proliferation and apoptosis in the livers of rats fed a choline-deficient, L-amino acid-defined diet."Hepatol Res. 28. 94-101 (2004)
Onaga M 等人:“喂食缺乏胆碱、L-氨基酸限定饮食的大鼠肝脏中生长因子的表达增强以及肝细胞增殖和凋亡之间的不平衡。”Hepatol Res。
  • DOI:
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    0
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  • 通讯作者:
Ido A, et al.: "HGF hepatic regenerative therapy. (in Japanese)"Saishin Igaku. 58(9). 2023-2029 (2003)
Ido A 等人:“HGF 肝再生疗法。(日语)”Saishin Igaku。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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  • 通讯作者:
Moriuchi A, et al.: "A cre and the region ocupied by a protein induced by growth factors cintribute to up-regulation of cyclin D1 expression in hepatocytes."Biochem Biophys Res Commun. 300-2. 415-421 (2003)
Moriuchi A 等人:“Cre 和由生长因子诱导的蛋白质占据的区域有助于肝细胞中细胞周期蛋白 D1 表达的上调。”Biochem Biophys Res Commun。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Moriuchi A, Ido A, et al.: "A CRE and the region occupied by a protein induced by growth factors contribute to up-regulation of cyclin D1 expression in hepatocytes"Biochemical and Biophysical Research Communications. 300・2. 415-421 (2003)
Moriuchi A、Ido A 等人:“CRE 和生长因子诱导的蛋白质占据的区域有助于肝细胞中细胞周期蛋白 D1 表达的上调”《生物化学和生物物理研究通讯》300・2。 2003)
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    0
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TSUBOUCHI Hirohito其他文献

TSUBOUCHI Hirohito的其他文献

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{{ truncateString('TSUBOUCHI Hirohito', 18)}}的其他基金

Involvement of apoptosis inhibitory factor of macrophage (AIM) on pathophysiological condition of chronic liver disease
巨噬细胞凋亡抑制因子(AIM)对慢性肝病病理生理的影响
  • 批准号:
    26670385
  • 财政年份:
    2014
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Analysis for molecular mechanism of hepatitis C virus(HCV)-induced protein associated with persistent HCV infection
丙型肝炎病毒(HCV)诱导蛋白与HCV持续感染相关的分子机制分析
  • 批准号:
    24659371
  • 财政年份:
    2012
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Using proteomics to elucidate pathogenesis and establish new diagnostic or treatment evaluation methods in refractory gastrointestinal diseases
利用蛋白质组学阐明难治性胃肠道疾病的发病机制并建立新的诊断或治疗评估方法
  • 批准号:
    23249043
  • 财政年份:
    2011
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
A role of hepatocyte growth factor in regulation of hepatic development and differentiation
肝细胞生长因子在肝脏发育和分化调控中的作用
  • 批准号:
    19209028
  • 财政年份:
    2007
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
A transcriptional factor induced by HGF
HGF 诱导的转录因子
  • 批准号:
    10470138
  • 财政年份:
    1998
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
Injured Tissue Specific HGF Expression and its Mechanism
损伤组织特异性HGF表达及其机制
  • 批准号:
    08457171
  • 财政年份:
    1996
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Identification of HGF indncing factor in serum from patients with Liver diseases
肝病患者血清中HGF诱导因子的鉴定
  • 批准号:
    05454247
  • 财政年份:
    1993
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)

相似海外基金

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预测肝细胞癌肝干细胞特征及上皮间质转化特征的影像学生物标志物研究
  • 批准号:
    15K19780
  • 财政年份:
    2015
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Studies on molecular mechanisms regulating fate decision of hepatic stem cells and efficacy of hepatic stem cell transplantation
肝干细胞命运决定的分子机制及肝干细胞移植疗效研究
  • 批准号:
    24590957
  • 财政年份:
    2012
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    $ 9.02万
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Analysis of hepatic stem cell specific histone modifications as a basis for identification of molecular targets to block hepatic carcinogenesis
分析肝干细胞特异性组蛋白修饰作为识别阻断肝癌发生的分子靶点的基础
  • 批准号:
    23791491
  • 财政年份:
    2011
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Regeneration of Fibrotic Liver through Modulation of Hepatic Stem Cell Niche and Differentiation of Bone Marrow Stem Cells
通过调节肝干细胞生态位和骨髓干细胞分化实现纤维化肝脏的再生
  • 批准号:
    22390152
  • 财政年份:
    2010
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Development of New Strategy of Immunological Tolerance Inductionby Intraportal administration of donor specific Mesenchymal hepatic stem cell in OrganTransplantation
器官移植中供体特异性间充质肝干细胞门静脉注射诱导免疫耐受新策略的开发
  • 批准号:
    21390356
  • 财政年份:
    2009
  • 资助金额:
    $ 9.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Research on molecular mechanism of hepatic stem cell proliferation and development of mouse models for stem cell transplantation
肝干细胞增殖分子机制研究及干细胞移植小鼠模型的建立
  • 批准号:
    20790485
  • 财政年份:
    2008
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The verification for plasticity of hepatic stem cell by using functional analysis of embryonic stem cell and organ-specific stem cell
利用胚胎干细胞和器官特异性干细胞的功能分析验证肝干细胞的可塑性
  • 批准号:
    19591580
  • 财政年份:
    2007
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    $ 9.02万
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The roles of polycomb-group proteins in hepatic stem cell self-renewal and carcinogenesis.
多梳族蛋白在肝干细胞自我更新和癌发生中的作用。
  • 批准号:
    19790946
  • 财政年份:
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Therapeutic Strategy for Diabrtes mellitus by Hepatic Stem cell
肝干细胞治疗糖尿病的策略
  • 批准号:
    19209045
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    2007
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Proliferation and differentiation of hepatic stem cell from bone marrow cells and possibility of bone marrow transplantation in genetic hepatic disease
骨髓细胞肝干细胞的增殖分化及遗传性肝病骨髓移植的可能性
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    15591362
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    2003
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    $ 9.02万
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    Grant-in-Aid for Scientific Research (C)
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