Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy
Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy
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DOI：
10.1053/gast.2003.50097
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发表时间：
2003-03-01
期刊：
影响因子：
29.4
通讯作者：
Kohno, K
中科院分区：
文献类型：
--
作者：
Kiso, S;Kawata, S;Kohno, K
背景和目标：肝素结合表皮生长因子样生长因子（HB-EGF）是EGF家族的一员，以膜锚定前体（proHB-EGF）的形式合成，随后经蛋白水解加工成成熟的HB-EGF。本研究描述了HB-EGF对肝脏特异性表达的proHB-EGF转基因小鼠70%肝部分切除后肝再生的影响。方法和结果：成年转基因小鼠和野生型小鼠的肝/体重比和溴脱氧尿苷（BrdU）标记指数（BrdU阳性肝细胞核的比例）无显着差异。然而，在部分肝切除术后的再生肝中，转基因小鼠的肝/体重比高于野生型小鼠，并且在120小时达到与部分肝切除术前相同的水平。肝部分切除后48小时，转基因小鼠肝脏中BrdU标记指数约为野生型小鼠的5倍（分别为51.5%和10.2%; P < 0.01）。与野生型小鼠相比，部分肝切除术后转基因小鼠中微管相关蛋白激酶的激活更高且更早。肝部分切除术后8分钟，肝组织中可溶性HB-EGF增加，表明肝部分切除术后发生了proHB-EGF的脱落。结论：HB-EGF的转基因表达促进了部分肝切除后肝细胞的增殖，表明HB-EGF在体内起着肝营养因子的作用。
Background & Aims: Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family, is synthesized in the form of a membrane-anchored precursor (proHB-EGF), which subsequently is processed proteolytically to mature HB-EGF. This study describes the effects of HB-EGF on liver regeneration after 70% partial hepatectomy in proHB-EGF transgenic mice with liver-specific expression. Methods & Results: No significant differences in liver/body weight ratios and in bromodeoxyuridine (BrdU)-labeling index (the ratios of BrdU-positive hepatocyte nuclei) were found between adult transgenic and wild-type mice. However, in regenerating liver after partial hepatectomy, transgenic mice had higher liver/body weight ratios than wild-type mice and at 120 hours reached a level equal to that before partial hepatectomy. The BrdU-labeling index was about 5 times higher in the livers of transgenic mice compared with the wild type (51.5% vs. 10.2%, respectively; P < 0.01) at 48 hours after partial hepatectomy. Activation of microtubule-associated protein kinase after partial hepatectomy was higher and earlier in the transgenic mice as compared with the wild-type mice. Soluble HB-EGF was increased in the liver (at 8 min) after partial hepatectomy, indicating that the shedding of proHB-EGF occurred after partial hepatectomy. Conclusions: The transgenic expression of HB-EGF accelerates the proliferation of hepatocytes after partial hepatectomy, suggesting that HB-EGF functions as a hepatotrophic factor in vivo.