武汉云克隆科技股份有限公司

Abstract:

The acute phase protein orosomucoid-1 (Orm1) is mainly expressed by hepatocytes (HPCs) under stress conditions. However, its specific function is not fully understood. Here, we report a role of Orm1 as an executer of HPC proliferation. Increases in serum levels of Orm1 were observed in patients after surgical resection for liver cancer and in mice undergone partial hepatectomy (PH). Transcriptome study showed that Orm1 became the most abundant in HPCs isolated from regenerating mouse liver tissues after PH. Both in vitro and in vivo siRNA-induced knockdown of Orm1 suppressed proliferation of mouse regenerating HPCs and human hepatic cells. Microarray analysis in regenerating mouse livers revealed that the signaling pathways controlling chromatin replication, especially the minichromosome maintenance protein complex genes were uniformly down-regulated following Orm1 knockdown. These data suggest that Orm1 is induced in response to hepatic injury and executes liver regeneration by activating cell cycle progression in HPCs.

摘要：

应激条件下急性类粘蛋白1(Orm1)主要由肝细胞(HPCs)表达。然而，它的具体功能还没有得到充分的理解。本研究探讨了Orm 1作为高密度脂蛋白(HPC)增殖执行者的作用。在肝癌患者和部分肝切除（pH）小鼠模型中观察到血清ORM1水平升高。转录组学研究表明，小鼠部分肝切除后，从小鼠再生肝组织中分离出的HPC中Orm1含量最高。体外和体内siRNA诱导的Orm1基因敲除会抑制小鼠再生肝细胞和人肝细胞的增殖。小鼠肝脏再生过程中的微阵列分析表明，染色质复制的信号通路是由信号传导途径控制的，特别当Orm1基因敲除后，微小染色体维持蛋白复合体基因的表达均下降。研究数据揭示了Orm1是对肝损伤的反应，通过激活HPCs细胞周期进程来实现肝细胞再生。

使用试剂原文信息:

Serum Orm1 concentrations were measured using ELISA kits (SEA816HU and SEA816MU for human and mouse serum samples, respectively; Cloud-Clone Corp., Houston, TX, USA).

For mouse liver sections, after blocking with 5% normal goat serum in PBS containing 0.1% Tween-20 (PBST) for 30 min at room temperature, the sections were incubated with rabbit anti-mouse Orm1 (2ug/mL; PAA816Mu01; Cloud-Clone Corp) or control rabbit IgG overnight at 4℃.

After blocking with 5% FBS-PBS for 1h at room temperature, cells were incubated with rabbit anti-mouse Orm1 antibody (1ug/mL; PAA816Mu01; Cloud-Clone Corp) or control rabbit IgG overnight at 4℃.