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Effect of HB-EGF on liver regeneration in vovo and its application as a therapeutic agent.

HB-EGF 对体内肝再生的影响及其作为治疗剂的应用。

基本信息

批准号：
09670544
负责人：
TAMURA Shinji
金额：
$ 1.92万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670544/
关键词：
HB-EGF liver regeneration hepatocyte growth factor in vivo therapy HB-EGF 肝産生マウス

项目摘要

We have reported that heparin-binding EGF-like growth factor(HB-EGF) is a potent mitogen of hepatocytes in vitro.The level of HB -EGF mRNA in regenerating rat liver increases rapidly after a partial hepatectomy.In vitro study showed that HB-EGF induces the expression of HGF and TGF-alpha in non-parenchymal cells and hepatocytes, respectively.These results indicated that HB-EGF may play an important role in liver regeneration.In this study, we investigated the plasma HB-EGF levels in patients after partial hepatectomy using enzyme-linked immunosorbent assay.In patients who underwent gross hepatectomy, plasma HB-EGF levels increased, reaching maximal levels approximately 5 to 7 days after surgery, which indicated that HB-EGF may be involved in liver regeneration in human.We also investigated the effect of administration HB-EGF to mice on proliferation of hepatocyte in vivo.Recombinant HB-EGF were administered intravenously to the normal mice for 4 times at 2h-interval.Proliferation of hepatocyte were determined as labeling index of BrdU.Activation of NE-kB and STAT-3 were studied using gel shift assay.The labeling index is 300-fold higher in HB-EGF administered mice than that of controls.In vivo administration of HB-EGF activated NF-kB and STAT-3 in the liver. The induction of HGF were observed in HB-EGF-administered mice liver.In summary, in vivo administration of HB-EGF stimulated liver regeneration in normal mice liver, which indicated that HB-EGF could be a therapeutic agent for liver regeneration.

我们报道了肝素结合EGF样生长因子（HB-EGF）是一种有效的体外肝细胞有丝分裂原。在大鼠部分肝切除后的再生肝中HB-EGF mRNA水平迅速增加。体外研究表明HB-EGF分别诱导非实质细胞和肝细胞表达HGF和TGF-α。这些结果表明HB-EGF可能在肝再生中起重要作用。本研究中，我们用酶联免疫吸附试验研究了部分肝切除术后患者的血浆HB-EGF水平，在接受大体肝切除术的患者中，血浆HB-EGF水平升高，在手术后约5 - 7天达到最高水平，提示HB-EGF可能参与了人肝再生的过程，并观察了HB-EGF对人肝再生的影响。重组HB-EGF对正常小鼠肝细胞增殖的影响，以BrdU标记肝细胞增殖为指标，观察重组HB-EGF对NE-κ B和STAT-κ B的激活作用，并观察重组HB-EGF对肝细胞增殖的影响。结果表明，HB-EGF能激活肝脏中的NF-κ B和STAT-3，并能激活肝脏中的NF-κ B和STAT-3。HB-EGF可诱导正常小鼠肝细胞产生HGF，提示HB-EGF可作为肝再生的治疗剂。