Impaired liver regeneration in acute liver failure: the significance of cross‐communication of growth associated factors in liver regeneration
Impaired liver regeneration in acute liver failure: the significance of cross‐communication of growth associated factors in liver regeneration
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DOI：
10.1111/j.1872-034x.2008.00423.x
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发表时间：
2008-11
影响因子：
4.2
通讯作者：
T. Tomiya;M. Omata;H. Imamura;K. Fujiwara
中科院分区：
文献类型：
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作者：
T. Tomiya;M. Omata;H. Imamura;K. Fujiwara
在急性肝功能衰竭患者中，肝再生被认为是迟缓或被抑制的。然而，这种抑制的机制仍有待阐明。为了评估急性肝衰竭患者在肝再生方面的缺陷，我们在实验模型中重点研究了生长相关因子的交叉交流。在原代培养的大鼠肝细胞中，加入肝细胞生长因子(HGF)后，细胞内P53和转化生长因子-α(TGF-α)水平及DNA合成均增加。当P53活性被抑制时，转化生长因子-α的表达和DNA合成减少。当转化生长因子-α活性被抑制时，DNA合成也减少。大鼠肝部分切除后，肝组织HGF和P53蛋白水平升高，肝组织转化生长因子-α水平升高，肝细胞增殖。循环中的HGF和转化生长因子-α水平与肝脏水平的变化相关。抑制转化生长因子-α活性可抑制肝细胞的增殖。在急性肝炎患者中，血清HGF水平随着血清转化生长因子-α水平的升高而升高。相反，在急性肝功能衰竭患者中，尽管血清HGF水平显著升高，但血清转化生长因子-α水平的升高取决于肝功能衰竭的严重程度。患者的肝脏水平与血清水平一致。生长相关因子的交叉传递在肝脏再生的进展中可能是重要的，急性肝功能衰竭患者的再生能力受损可能至少部分归因于生长相关因子的传递中断。
Liver regeneration is considered to be retarded or suppressed in patients with acute liver failure. However, the mechanisms for this suppression remain to be elucidated. In order to evaluate deficiencies in liver regeneration in patients with acute liver failure, we focused on the cross‐communication of growth‐associated factors in experimental models. In primary cultured rat hepatocytes, the levels of cellular p53 and transforming growth factor‐alpha (TGF‐alpha), as well as DNA synthesis increased by the addition of hepatocyte growth factor (HGF). When p53 activity was suppressed, TGF‐alpha expression and DNA synthesis were reduced. DNA synthesis was also reduced when TGF‐alpha activity was suppressed. In rats after partial hepatectomy, hepatic HGF and p53 protein levels increased, followed by an increase of hepatic TGF‐alpha levels and hepatocyte proliferation. Circulating levels of HGF and TGF‐alpha correlated with changes in the hepatic levels. The suppression of TGF‐alpha activity reduced the proliferation of hepatocytes in these rats. In patients suffering from acute hepatitis, serum HGF levels increased followed by an increase of serum TGF‐alpha levels. In contrast, in patients with acute liver failure, the increase of serum TGF‐alpha levels was suppressed depending on the severity of hepatic failure, even though serum HGF levels markedly increased. The patients' hepatic levels were consistent with serum levels. Cross‐communication of growth associated factors may be important in the progression of liver regeneration, and impaired regenerative capacity in patients with acute liver failure may be attributable, at least in part, to a disruption of communication of growth‐associated factors.