Liver regeneration was affected by carboxylase gene transfer.

在目前的研究中，我们研究了基因转移在肝脏再生中的作用。谷氨酰羧基酶(GGCX)是DES-γ-羧基凝血酶原(DCP)转化为正常凝血酶原的限速酶。DCP对Hep3B和SK-Hep-1细胞的增殖活性有1.5~2.0倍的刺激作用。这种作用是通过激活Met-JAK1-STAT3信号通路实现的。DCP刺激人脐静脉内皮细胞(HUVEC)。DCP可使HUVEC的细胞迁移活性和增殖活性分别提高2.2倍和1.5倍。这种作用是通过激活磷脂酶-C-γ和ERK-MAPK来实现的。用RT-PCR方法从肝细胞癌细胞系中克隆了变异型GGCX基因。变异型GGCX基因的导入将DCP阴性的细胞系转化为DCP产生细胞。导入针对GGCX的siRNA与导入变异型GGCX的效果相同。这些细胞表现出促进细胞迁移和增殖。综上所述，引入异型GGCX和针对GGCX的siRNA可能是控制肝再生过程中肝细胞增殖和血管生成的有效策略。

In the current study, we investigate the effect of gene transfer in liver regeneration. Gamma-glutamyl carboxylase (GGCX) is known as a rate-limiting enzyme in the conversion of des-gamma-carboxy prothrombin (DCP) into normal prothrombin. DCP stimulated cell proliferative activities 1.5-2.0 fold in Hep3B and SK-Hep-1 cells. This effect was brought through activation of Met-JAK1-STAT3 signaling pathway. Moreover, DCP stimulated human umbilical vein endothelial cells (HUVEC). The cell migrative activity and cell proliferative activity were enhanced 2.2 fold and 1.5 fold, respectively by DCP in HUVEC. This effect was caused by activation of phospholipase-C-γ and erk-MAPK. Variant type of GGCX was cloned from hepatocellular carcinoma cell line by RT-PCR. Introduction of variant type-GGCX cDNA converted DCP-negative cell lines into DCP-producing cells. Introduction of siRNA against GGCX showed same effect as introduction of variant type-GGCX. These cells showed enhanced cell migration and proliferation. In conclusion, introduction of variant type-GGCX and siRNA against GGCX might be an effective strategy to control cell proliferation of hepatocyte and angiogenesis in liver regeneration.