肝细胞生长因子对大鼠肝细胞的促有丝分裂活性依赖于内源性转化生长因子-α。
The mitogenic activity of hepatocyte growth factor on rat hepatocytes is dependent upon endogenous transforming growth factor-alpha.
作者信息
Tomiya T, Ogata I, Yamaoka M, Yanase M, Inoue Y, Fujiwara K
机构信息
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
出版信息
Am J Pathol. 2000 Nov;157(5):1693-701. doi: 10.1016/s0002-9440(10)64806-7.
Both transforming growth factor-alpha (TGF-alpha) and hepatocyte growth factor (HGF) induce DNA synthesis in hepatocytes in vitro and in vivo. Hepatic and circulating levels of HGF have been reported to increase before an increase in TGF-alpha levels in several rat models of liver regeneration. In addition, serum TGF-alpha levels increase after an increase in serum HGF levels in patients with either partial hepatectomy or acute hepatitis. In this study, we investigate the significance of TGF-alpha in hepatocyte proliferation. TGF-alpha contents and DNA synthesis in cultured rat hepatocytes increased in response to HGF addition to the culture medium in a dose-related manner. These increases were suppressed by the addition of anti-sense TGF-alpha mRNA oligonucleotide. Furthermore, the addition of anti-TGF-alpha rabbit IgG suppressed the increase in DNA synthesis. When the anti-TGF-alpha antibody was administered to rats after partial hepatectomy, the number of mitotic hepatocytes was reduced in comparison to rats treated with normal rabbit IgG. These results were observed even though hepatic HGF levels were increased equally in rats given either anti-TGF-alpha antibody or normal rabbit IgG. Our results suggest that HGF stimulates TGF-alpha production in rat hepatocytes, and that the mitogenic activity of HGF depends on endogenous TGF-alpha activity.
转化生长因子-α（TGF-α）和肝细胞生长因子（HGF）在体内外均可诱导肝细胞的DNA合成。在几种肝再生大鼠模型中，据报道HGF的肝脏和循环水平在TGF-α水平升高之前就已升高。此外，在接受部分肝切除术或患有急性肝炎的患者中，血清HGF水平升高后血清TGF-α水平也会升高。在本研究中，我们调查了TGF-α在肝细胞增殖中的意义。向培养基中添加HGF后，培养的大鼠肝细胞中的TGF-α含量和DNA合成呈剂量相关增加。添加反义TGF-α mRNA寡核苷酸可抑制这些增加。此外，添加抗TGF-α兔IgG可抑制DNA合成的增加。部分肝切除术后给大鼠注射抗TGF-α抗体，与用正常兔IgG处理的大鼠相比，有丝分裂肝细胞的数量减少。即使给予抗TGF-α抗体或正常兔IgG的大鼠肝脏HGF水平同样升高，也观察到了这些结果。我们的结果表明，HGF刺激大鼠肝细胞中TGF-α的产生，并且HGF的促有丝分裂活性取决于内源性TGF-α活性。
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