PDF(Pubmed)
Abstract：
Liver regeneration induced by partial hepatectomy (PHx) has attracted intensive research interests due to the great significance for liver resection and transplantation. The zebrafish (Danio rerio) is an excellent model to study liver regeneration. In the fish subjected to PHx (the tip of the ventral lobe was resected), the lost liver mass could be fully regenerated in seven days. However, the regulatory mechanisms underlying the liver regeneration remain largely unknown. In this study, gene expression profiles during the regeneration of PHx-treated liver were explored by RNA sequencing (RNA-seq). The genes responsive to the injury of PHx treatment were identified and classified into different clusters based on the expression profiles. Representative gene ontology (GO) enrichments for the early responsive genes included hormone activity, ribosome biogenesis and rRNA processing, etc., while the late responsive genes were enriched in biological processes such as glutathione metabolic process, antioxidant activity and cellular detoxification. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments were also identified for the differentially expressed genes (DEGs) between the time-series samples and the sham controls. The proteasome was overrepresented by the up-regulated genes at all of the sampling time points. Inhibiting proteasome activity by the application of MG132 to the fish enhanced the expression of Pcna (proliferating cell nuclear antigen), an indicator of hepatocyte proliferation after PHx. Our data provide novel insights into the molecular mechanisms underlying the regeneration of PHx-treated liver.
摘要：
肝部分切除术（PHx）诱导的肝再生由于对肝切除和移植的重要意义而引起了广泛的研究兴趣。斑马鱼（Daniorerio）是研究肝脏再生的极好模型。在接受PHx的鱼中（切除了腹叶的尖端），丢失的肝脏可以在七天内完全再生。然而,肝脏再生的调节机制在很大程度上仍然未知.在这项研究中,通过RNA测序(RNA-seq)探索PHx处理肝脏再生过程中的基因表达谱.鉴定对PHx处理的损伤有反应的基因，并根据表达谱分为不同的簇。早期反应基因的代表性基因本体论(GO)富集包括激素活性，核糖体生物发生和rRNA加工，等。,而晚期反应基因在生物过程如谷胱甘肽代谢过程中富集，抗氧化活性和细胞解毒。还鉴定了时间序列样品和假对照之间的差异表达基因(DEGG)的京都基因和基因组百科全书(KEGG)途径富集。蛋白酶体在所有采样时间点被上调的基因过度代表。通过对鱼类应用MG132抑制蛋白酶体活性增强了Pcna（增殖细胞核抗原）的表达，PHx后肝细胞增殖的指标。我们的数据为PHx处理的肝脏再生的分子机制提供了新的见解。
