ROLE OF HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH-FACTOR AS A HEPATOTROPHIC FACTOR IN RAT-LIVER REGENERATION AFTER PARTIAL-HEPATECTOMY
ROLE OF HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH-FACTOR AS A HEPATOTROPHIC FACTOR IN RAT-LIVER REGENERATION AFTER PARTIAL-HEPATECTOMY
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DOI：
10.1016/0270-9139(95)90168-x
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发表时间：
1995-11-01
期刊：
影响因子：
13.5
通讯作者：
MATSUZAWA, Y
中科院分区：
文献类型：
--
作者：
KISO, S;KAWATA, S;MATSUZAWA, Y
包括肝细胞生长因子（HGF）在内的几种生长因子已经涉及肝再生的调节。最近，我们报道了肝素结合表皮生长因子（EGF）样生长因子（HB-EGF）在体外具有促肝作用。我们研究了HB-EGF作为肝营养因子在大鼠70%肝部分切除后再生肝脏中的作用。部分肝切除术后1.5小时，再生大鼠肝脏中HB-EGF信使RNA（mRNA）水平升高，并在6小时达到最大值（约为正常水平的7倍）。相反，肝HGF mRNA水平在12小时增加，并在24小时达到最大表达。肝部分切除后10小时HB-EGF蛋白表达较正常增加2.8倍，肝部分切除后6小时HB-EGF结合的EGF受体数量减少。肝部分切除后6小时，非实质细胞（NPC）中HB-EGF mRNA水平升高，但肝细胞中无此变化。用逆转录-聚合酶链反应（RT-PCR）技术检测了HB-EGF基因在枯否细胞和肝窦内皮细胞中的表达，而在脂肪细胞和肝细胞中的表达无明显变化。结果表明，HB-EGF可能是肝部分切除后再生肝的一种重要的生长因子，其产生于再生肝的早期阶段，而不是HGF。
Several growth factors including hepatocyte growth factor (HGF) have been implicated in the regulation of liver regeneration. Recently, we reported that heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) has hepatotrophic effects in vitro. We investigated the role of HB-EGF as a hepatotrophic factor in regenerating rat liver after 70% partial hepatectomy. The level of HB-EGF messenger RNA (mRNA) in regenerating rat liver increased 1.5 hours after partial hepatectomy and reached a maximum (about sevenfold over normal) at 6 hours. In contrast, hepatic HGF mRNA levels increased at 12 hours and achieved maximal expression at 24 hours. HB-EGF protein expression increased about 2.8-fold over normal at 10 hours after partial hepatectomy, The number of EGF receptors, to which HB-EGF binds, decreased 6 hours after partial hepatectomy. HB-EGF mRNA levels increased in nonparenchymal cells (NPCs) at 6 hours after partial hepatectomy but not in hepatocytes. Using the reverse transcription-polymerase chain reaction (RT-PCR), HB-EGF gene expression was increased predominantly in Kupffer cells and sinusoidal endothelial cells but not in lipocytes and hepatocytes, These results indicated that HB-EGF may be an important growth factor, produced in an earlier phase rather than HGF, in the regenerating liver after partial hepatectomy by a paracrine mechanism.