Characterization of growth-differentiation factor 15, a transforming growth factor β superfamily member induced following liver injury
Characterization of growth-differentiation factor 15, a transforming growth factor β superfamily member induced following liver injury
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DOI：
10.1128/mcb.20.10.3742-3751.2000
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发表时间：
2000-05-01
影响因子：
5.3
通讯作者：
Lee, SJ
中科院分区：
文献类型：
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作者：
Hsiao, EC;Koniaris, LG;Lee, SJ
我们已经确定了一个新的小鼠转化生长因子β超家族成员，生长分化因子15 (Gdf15)，在成人肝脏中表达水平最高。Northern的分析表明，在各种外科和化学治疗导致急性肝损伤和再生后，肝脏中Gdf15的表达迅速而显著地上调。原位杂交分析揭示了Gdf15 mRNA定位的不同模式，这似乎反映了每种实验处理中已知的肝细胞损伤模式。此外，用四氯化碳或热休克处理两种肝细胞样细胞系可诱导Gdf15 mRNA表达，这表明直接细胞损伤可在没有其他细胞类型（如炎症细胞）的情况下诱导Gdf15表达。为了研究Gdf15的潜在功能，我们通过基因靶向建立了Gdf15缺失小鼠。尽管在部分肝切除和四氯化碳损伤模型中观察到Gdf15表达的显著调节，但我们发现纯合null突变体和野生型小鼠在损伤反应上没有差异。我们的研究结果表明，要么Gdf15在肝损伤和再生中没有调节作用，要么Gdf15在肝脏中的功能与其他信号分子的功能是多余的。
We have identified a new murine transforming growth factor beta superfamily member, growth-differentiation factor 15 (Gdf15), that is expressed at highest levels in adult liver. As determined by Northern analysis, the expression of Gdf15 in liver was rapidly and dramatically up-regulated following various surgical and chemical treatments that cause acute liver injury and regeneration. In situ hybridization analysis revealed distinct patterns of Gdf15 mRNA localization that appeared to reflect the known patterns of hepatocyte injury in each experimental treatment. In addition, treatment of two hepatocyte-like cell lines with either carbon tetrachloride or heat shock induced Gdf15 mRNA expression, indicating that direct cellular injury can induce Gdf15 expression in the absence of other cell types, such as inflammatory cells, In order to investigate the potential functions of Gdf15, we created Gdf15 null mice by gene targeting. Homozygous null mice were viable and fertile, Despite the dramatic regulation of Gdf15 expression observed in the partial-hepatectomy and carbon tetrachloride injury models, we found no differences in the injury responses between homozygous null mutants and wild-type mice. Our findings suggest either that Gdf15 does not have a regulatory role in liver injury and regeneration or that Gdf15 function within the liver is redundant with that of other signaling molecules.