Enhancement of albumin production by hepatocyte growth factor in rat hepatocytes: distinction in mode of action from stimulation of DNA synthesis.

Enhancement of albumin production by hepatocyte growth factor in rat hepatocytes: distinction in mode of action from stimulation of DNA synthesis.
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肝细胞生长因子在大鼠肝细胞中增强白蛋白产生:作用方式与刺激 DNA 合成的区别。

DOI:
10.1111/j.1600-0676.1998.tb00127.x
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发表时间:
2008
期刊:
Liver
影响因子:
--
通讯作者:
K. Fujiwara
K. Fujiwara
中科院分区:
--
文献类型:
--
作者:
M. Yamaoka;K. Hirata;I. Ogata;T. Tomiya;S. Nagoshi;S. Mochida;K. Fujiwara

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肝细胞生长因子(HGF)被证明可以促进白蛋白的产生,并刺激肝细胞DNA的合成。HGF在这两种作用中的作用机制尚待阐明。我们曾观察到静脉注射重组人肝细胞生长因子(RhHGF)的正常大鼠肝细胞发生增殖。当大鼠接受类似的重组人肝细胞生长因子治疗时,血清白蛋白水平显著高于对照组。在原代培养的大鼠肝细胞中,加入重组人肝细胞生长因子后,培养24 h时,培养液中的白蛋白浓度明显高于对照组,且随培养时间的延长而增加。重组人肝细胞生长因子的这种作用与剂量有关。在培养液中加入放线菌素D后,白蛋白浓度呈剂量依赖性降低,而重组人肝细胞生长因子对白蛋白浓度的增强作用保持不变。重组人肝细胞生长因子对白蛋白基因表达无明显影响。当加入与培养液相似的rhHGF时,30h后出现5-溴-2‘-脱氧尿苷(BrdU)掺入免疫细胞化学阳性的肝细胞。在这些标记的肝细胞中,12.5%的细胞同时被白蛋白染色。相比之下,在未标记BrdU的肝细胞中,77%的肝细胞呈白蛋白阳性(p<0.01)。我们得出结论,HGF可能通过转录后调节在非增殖性肝细胞中增加白蛋白的产生,但在增殖性肝细胞中不能。
Hepatocyte growth factor (HGF) has been shown to enhance albumin production as well as stimulate DNA synthesis in hepatocytes. The mode of action of HGF in exerting both effects is to be elucidated. We previously observed that hepatocyte proliferation occurred in normal rats given recombinant human HGF (rhHGF) intravenously. When rats received rhHGF similarly, serum albumin levels were significantly increased compared to controls. In primary culture of rat hepatocytes, albumin concentration in culture medium was significantly increased by rhHGF added at 24 h of culture compared to controls, increasing with time of culture. This effect of rhHGF was dose-related. When actinomycin D was added to the medium, the albumin concentration was reduced in a dose-related manner, but its enhancement by rhHGF was maintained. Albumin mRNA levels were not increased by rhHGF. When rhHGF was added similarly to the medium, immunocytochemically positive hepatocytes for 5-bromo-2'-deoxyuridine (BrdU) incorporation appeared 30 h later. Of these labeled hepatocytes, 12.5% were concomitantly stained for albumin. In contrast, albumin-positive hepatocytes were seen in 77% of BrdU-non-labeled hepatocytes (p<0.01). We conclude that HGF may enhance albumin production through post-transcriptional regulation in non-proliferating hepatocytes, but not in proliferating hepatocytes.
在四氯化碳诱导肝再生过程中从白蛋白到甲胎蛋白的转录转换以及其他基因转录的变化。
DOI: 10.1021/bi00354a034
发表时间: 1986
期刊: Biochemistry
影响因子: 2.9
作者:
Panduro,A;Shalaby,F;Weiner,FR;Biempica,L;Zern,MA;Shafritz,DA
通讯作者: Shafritz,DA