Interleukin-6/glycoprotein 130-dependent pathways are protective during liver regeneration
Interleukin-6/glycoprotein 130-dependent pathways are protective during liver regeneration
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DOI：
10.1074/jbc.m208470200
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发表时间：
2003-03-28
影响因子：
4.8
通讯作者：
Trautwein, C
中科院分区：
文献类型：
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作者：
Wuestefeld, T;Klein, C;Trautwein, C
在组织丢失后，肝脏具有通过肝细胞增殖来恢复体积的独特能力。白细胞介素-6 （IL6）缺陷小鼠在部分肝切除术（PH）后显示DNA合成缺乏。为了更好地确定IL6及其家族成员在PH后肝脏再生中的作用，我们使用条件敲除小鼠糖蛋白130 (gp130)，这是所有IL6家族成员的共同信号传感器。我们发现gp130依赖通路控制ph后Stat3的激活。通过基因阵列分析，我们发现c-jun、NF-kappaB、c-myc和肿瘤坏死因子受体的表达是gp130依赖的。然而，与对照组相比，在gp130缺失的小鼠中，PH后对细胞周期和DNA合成最大值的影响较小。在条件gp130动物中，急性期反应完全消失，我们认为其他方法对于确定gp130依赖性途径在肝脏再生中的作用至关重要。PH后gp130缺失和IL6 -/-的LPS刺激导致存活和DNA合成显著降低，这与肝脏Bcl-xL表达降低和细胞凋亡增加有关。这些结果表明，与DNA合成减少有关的表型可能与ph后的感染程度有关。因此，我们的研究结果表明，gp130依赖信号的作用并不直接影响部分肝切除术后的细胞周期进展，而是激活对肝细胞增殖至关重要的保护途径。
After tissue loss the liver has the unique capacity to restore its mass by hepatocyte proliferation. Interleukin-6 (IL6)-deficient mice show a lack in DNA synthesis after partial hepatectomy (PH). To define better the role of IL6 and its family members for liver regeneration after PH, we used conditional knockout mice for glycoprotein 130 (gp130), the common signal transducer of all IL6 family members. We show that gp130-dependent pathways control Stat3 activation after PH. By using gene array analysis, we demonstrate that c-jun, NF-kappaB, c-myc, and tumor necrosis factor receptor expression is gp130-dependent. However, in gp130-deleted mice only minor effects on cell cycle and on the maximum of DNA synthesis after PH were found compared with controls. As in conditional gp130 animals, the acute phase response was completely abolished, we considered that other means are essential to define the role of gp130-dependent pathways for liver regeneration. LPS stimulation in gp130-deleted and also IL6 -/- animals after PH leads to a significant reduction in survival and DNA synthesis, which was associated with decreased Bcl-xL expression and higher apoptosis in the liver. These results indicate that the phenotype concerning the reduction in DNA synthesis might be linked to the degree of infection after PH. Thus our results suggest that the role of gp130-dependent signaling is not a direct influence on cell cycle progression after partial hepatectomy but is to activate protective pathways important to enable hepatocyte proliferation.