Identification and characterization of "injurin," an inducer of expression of the gene for hepatocyte growth factor.

Identification and characterization of "injurin," an inducer of expression of the gene for hepatocyte growth factor.
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“injurin”的鉴定和表征,“injurin”是肝细胞生长因子基因表达的诱导剂。

DOI:
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发表时间:
1992
影响因子:
11.1
通讯作者:
Toshikazu Nakamura
Toshikazu Nakamura
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kunio Matsumoto;H. Tajima;M. Hamanoue;S. Kohno;T. Kinoshita;Toshikazu Nakamura

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肝部分切除或单侧肾切除后大鼠完整肺组织中肝细胞生长因子(HGF)mRNA的显著快速增加,提示存在一种介导远端器官损伤信号的体液因子,并可能诱导这些器官中HGF基因的表达。我们现在已经确定了一种蛋白质因子在大鼠血清中的肝或肾损伤,增加肝细胞生长因子mRNA在完整的肺。将部分肝切除或缺血处理引起的肝损伤大鼠血清腹腔注射到正常非损伤大鼠中,可诱导受体大鼠肺中HGF mRNA的显著表达。在培养的MRC-5人胚肺成纤维细胞中加入各种肝或肾损伤大鼠的血清也可诱导HGF mRNA的表达,因此,用血清处理后的MRC-5细胞在培养基中的HGF产量显著增加。而正常大鼠血清在体内肺组织和体外肺成纤维细胞中均不诱导HGF的产生和HGF mRNA的表达。该因子,增加肝细胞生长因子的生产,纯化大于200倍,从四氯化碳处理的大鼠血清。该因子经SDS/PAGE电泳鉴定为一种酸热稳定蛋白,表观分子量为10-20 kDa。在对肝脏或肾脏进行各种损伤处理后,其在大鼠血浆中的活性在3-6小时内显著增加。这些结果表明,该因子特异性地出现在器官损伤大鼠的血液中,并可能通过增加HGF合成的潜力参与器官再生。由于该因子似乎介导多种器官损伤,我们将其命名为“损伤素”。"
The marked and rapid increase of hepatocyte growth factor (HGF) mRNA in the intact lung of rats after partial hepatectomy or unilateral nephrectomy suggests the existence of a humoral factor mediating a signal of injury to distal organs and may induce the expression of HGF gene in these organs. We have now identified a proteinous factor in the sera of rats with injury of liver or kidney that increases HGF mRNA in the intact lung. When the serum of rats with liver insult caused by partial hepatectomy or ischemic treatment was injected i.p. into normal noninjured rats, it induced a marked HGF mRNA expression in the lung of the recipient rats. The addition of serum from rats with various hepatic or renal injuries to MRC-5 human embryonic lung fibroblasts in culture also led to the induction of HGF mRNA expression, so that the production of HGF by MRC-5 cells after treatment with the sera was remarkably increased in the culture medium. However, serum from the normal intact rat induced no HGF production and no HGF mRNA in the lung in vivo and lung fibroblasts in vitro. This factor, which increases HGF production, was purified greater than 200-fold from sera of CCl4-treated rats. The factor proved to be an acid- and heat-stable protein with an apparent molecular mass of 10-20 kDa in SDS/PAGE. Its activity markedly increased within 3-6 hr in the plasma of rats after various treatments that injured the liver or kidney. These results suggest that the factor specifically appears in the blood of rats with organ injury and may be involved in organ regeneration through the potential to increase the synthesis of HGF. Since the factor seems to mediate various organ injuries, we named it "injurin."