Amphiregulin:: An early trigger of liver regeneration in mice
Amphiregulin:: An early trigger of liver regeneration in mice
复制标题
DOI：
10.1053/j.gastro.2004.11.006
复制
发表时间：
2005-02-01
期刊：
影响因子：
29.4
通讯作者：
Avila, MA
中科院分区：
文献类型：
--
作者：
Berasain, C;García-Trevijano, ER;Avila, MA
背景与目的：肝再生是肝切除或损伤后肝块修复的一种独特反应。在这一过程中触发的生存和增殖信号由细胞因子和生长因子组成的复杂网络有序地传递。表皮生长因子受体的激活被认为在肝脏再生中起重要作用。双调节蛋白是表皮生长因子家族的一员，在健康肝脏中无法检测到其表达。我们研究了双调节蛋白在肝损伤中的表达及其在肝部分切除术后肝再生中的作用。方法：检测双调节蛋白基因在健康、肝硬化人和大鼠肝脏、部分肝切除术后的啮齿动物肝脏再生和原代肝细胞中的表达。在离体肝细胞中研究了双调节蛋白的增殖作用和细胞内信号转导。在无双角调节蛋白的小鼠中，分析了双角调节蛋白在肝部分切除后肝再生中的体内作用。结果：双调节蛋白基因在慢性损伤的人和大鼠肝脏中表达，并在啮齿动物肝部分切除后快速诱导表达。在分离的肝细胞中，双调节蛋白的表达可被白细胞介素1 β和前列腺素E-2诱导，但不能被肝细胞生长因子、白细胞介素6或肿瘤坏死因子a诱导。我们发现双调节蛋白作为分离肝细胞的主要丝裂原，通过表皮生长因子受体起作用。最后，双调节蛋白缺失小鼠在部分肝切除后表现出受损的增殖反应。结论：我们的研究结果表明，双调节蛋白是一种早期反应生长因子，可能有助于肝脏再生的初始阶段。
Background & Aims: Liver regeneration is a unique response directed to restore liver mass after resection or injury. The survival and proliferative signals triggered during this process are conveyed by a complex network of cytokines and growth factors acting in an orderly manner. Activation of the epidermal growth factor receptor is thought to play an important role in liver regeneration. Amphiregulin is a member of the epidermal growth factor family whose expression is not detectable in healthy liver. We have investigated the expression of amphiregulin in liver injury and its role during liver regeneration after partial hepatectomy. Methods: Amphiregulin gene expression was examined in healthy and cirrhotic human and rat liver, in rodent liver regeneration after partial hepatectomy, and in primary hepatocytes. The proliferative effects and intracellular signaling of amphiregulin were studied in isolated hepatocytes. The in vivo role of amphiregulin in liver regeneration after partial hepatectomy was analyzed in amphiregulin-null mice. Results: Amphiregulin gene expression is detected in chronically injured human and rat liver and is rapidly induced after partial hepatectomy in rodents. Amphiregulin expression is induced in isolated hepatocytes by interleukin 1beta and prostagiandin E-2, but not by hepatocyte growth factor, interleukin 6, or tumor necrosis factor a.. We show that amphiregulin behaves as a primary mitogen for isolated hepatocytes, acting through the epidermal growth factor receptor. Finally, amphiregulin-null mice display impaired proliferative responses after partial liver resection. Conclusions, Our findings indicate that amphiregulin is an early-response growth factor that may contribute to the initial phases of liver regeneration.