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大鼠肝细胞生长因子的一级结构及其在肝损伤后肝脏再生过程中mRNA的诱导

Primary structure of rat hepatocyte growth factor and induction of its mRNA during liver regeneration following hepatic injury.

作者信息

Okajima A, Miyazawa K, Kitamura N

机构信息

Institute for Liver Research, Kansai Medical University, Japan.

出版信息

Eur J Biochem. 1990 Oct 24;193(2):375-81. doi: 10.1111/j.1432-1033.1990.tb19349.x.

DOI:10.1111/j.1432-1033.1990.tb19349.x
PMID:2146117
Abstract

Overlapping cDNA clones for rat hepatocyte growth factor (rHGF) were isolated by cross-hybridization with the cloned cDNA for human hepatocyte growth factor (hHGF) and the nucleotide sequence of the cDNA was determined. The entire primary structure of rHGF was deduced from the sequence. Comparison of the amino acid sequences between rat and human HGFs revealed that the two sequences are highly conserved throughout the protein structures, suggesting that rat and human HGFs may be functionally similar. Responses of the rHGF mRNA during liver regeneration in rats were examined by Northern blot hybridization analysis with the aid of the cDNA probe for rHGF. The mRNA levels increased in the liver and spleen but not in the kidney after administration of carbon tetrachloride. At the maximum level of induction, the rHGF mRNA increased in the liver about 4.5-fold over its normal level. The mRNA levels also increased in the liver and spleen after administration of D-galactosamine. On the other hand, no obvious increase of the mRNA was observed in the liver and spleen after partial hepatectomy. These observations suggest that HGF may function as a regulator of liver regeneration following hepatic injury caused by hepatotoxins.

摘要

通过与人肝细胞生长因子(hHGF)的克隆cDNA进行交叉杂交,分离出大鼠肝细胞生长因子(rHGF)的重叠cDNA克隆,并测定了该cDNA的核苷酸序列。从该序列推导了rHGF的完整一级结构。大鼠和人HGF氨基酸序列的比较表明,这两个序列在整个蛋白质结构中高度保守,提示大鼠和人HGF可能在功能上相似。借助rHGF的cDNA探针,通过Northern印迹杂交分析检测了大鼠肝再生过程中rHGF mRNA的反应。给予四氯化碳后,肝脏和脾脏中的mRNA水平升高,但肾脏中未升高。在诱导的最高水平,肝脏中的rHGF mRNA比正常水平增加了约4.5倍。给予D-半乳糖胺后,肝脏和脾脏中的mRNA水平也升高。另一方面,部分肝切除术后,肝脏和脾脏中未观察到mRNA明显增加。这些观察结果提示,HGF可能作为肝毒素引起的肝损伤后肝再生的调节因子发挥作用。

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