Initiation of liver growth by tumor necrosis factor: Deficient liver regeneration in mice lacking type I tumor necrosis factor receptor
Initiation of liver growth by tumor necrosis factor: Deficient liver regeneration in mice lacking type I tumor necrosis factor receptor
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DOI：
10.1073/pnas.94.4.1441
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发表时间：
1997-02-18
影响因子：
11.1
通讯作者：
Fausto, N
中科院分区：
文献类型：
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作者：
Yamada, Y;Kirillova, I;Fausto, N
为了确定细胞因子是否参与肝脏生长的启动，我们研究了缺乏I型肿瘤坏死因子受体（TNFR-I）的小鼠部分肝切除术（PH）后肝脏的再生，这些动物PH后DNA合成严重受损，预期PH后不久NF-kappa B和STAT3转录因子结合的增加未能发生。与受体完整的动物相比，PH后TNFR-I敲除小鼠的AP-1结合减少，而C/EBP结合未被改变。在PH前30分钟注射TNFR-I缺陷动物的白细胞介素6纠正了DNA合成缺陷，使STAT3和AP-1的结合恢复到正常水平，但对再生肝脏中nf - κ B的结合没有影响。可以启动肝脏再生，并通过激活涉及STAT3转录因子的白细胞介素6依赖性途径起作用。
The mechanisms that initiate liver regeneration after resection of liver tissue are not known, To determine whether cytokines are involved in the initiation of liver growth, we studied the regeneration of the liver after partial hepatectomy (PH) in mice lacking type I tumor necrosis factor receptor (TNFR-I), DNA synthesis after PH was severely impaired in these animals, and the expected increases in the binding of the NF-kappa B and STAT3 transcription factors shortly after PH failed to occur, Binding of AP-1 after PH was decreased in TNFR-I knockout mice compared with animals with the intact receptor whereas C/EBP binding was not modified, Injection of interleukin 6 in TNFR-I-deficient animals 30 min before PH corrected the defect in DNA synthesis and restored STAT3 and AP-1 binding to normal Levels but had no effect on NF-kappa B binding in the regenerating liver, The results indicate that TNF, signaling through the TNFR-I, can initiate Liver regeneration and acts by activating an interleukin 6-dependent pathway that involves the STAT3 transcription factor.