Liver regeneration was affected by carboxylase gene transfer.

肝再生受到羧化酶基因转移的影响。

• 批准号: 16390210
• 负责人: SHIRAHA Hidenori
• 金额: $ 8.9万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390210/
• 关键词: liver regeneration; angiogenesis; tumor marker

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.

在本研究中，我们研究了基因转移在肝再生中的作用。γ-谷氨酰羧化酶（GGCX）是脱-γ-羧基凝血酶原（DCP）转化为正常凝血酶原的限速酶。DCP刺激Hep 3B和SK-Hep-1细胞增殖活性1.5-2.0倍。这种作用是通过激活Met-JAK 1-STAT 3信号通路实现的。此外，DCP刺激人脐静脉内皮细胞（HUVEC）。DCP使HUVEC的细胞迁移活性和细胞增殖活性分别增强2.2倍和1.5倍。这种作用是由磷脂酶-C-γ和erk-MAPK激活引起的。应用RT-PCR技术从肝癌细胞株中克隆到GGCX的变异型。引入变体类型-GGCX cDNA将DCP阴性细胞系转化为DCP产生细胞。针对GGCX的siRNA的引入显示出与引入变体类型-GGCX相同的效果。这些细胞表现出增强的细胞迁移和增殖。因此，GGCX变异体的导入和针对GGCX的siRNA可能是控制肝细胞增殖和肝再生中血管生成的有效策略。

项目成果

Short-term high-dose followed by long-term low-dose hepatitis B immunoglobulin and lamivudine therapy prevented recurrent hepatitis B after liver transplantation

• DOI: 10.1097/01.tp.0000246310.75638.86
• 发表时间: 2007-01-27
• 期刊: TRANSPLANTATION
• 影响因子: 6.2
• 作者: Takaki, Akinobu;Yagi, Takahito;Shiratori, Yasushi
• 通讯作者: Shiratori, Yasushi

Establishment of hepatitis C virus replicon cell lines possessing interferon-resistant phenotype

• DOI: 10.1016/j.bbrc.2004.08.091
• 发表时间: 2004-10-08
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Namba, K;Naka, K;Kato, N
• 通讯作者: Kato, N

Antiviral therapy for cirrhotic hepatitis C: Association with reduced hepatocellular carcinoma development and improved survival

• DOI: 10.7326/0003-4819-142-2-200501180-00009
• 发表时间: 2005-01-18
• 期刊: ANNALS OF INTERNAL MEDICINE
• 影响因子: 39.2
• 作者: Shiratori, Y;Ito, Y;Omata, M
• 通讯作者: Omata, M

Des-gamma-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma.

• 发表时间: 2005
• 期刊: The Journal of biological chemistry
• 作者: Mayumi Suzuki;H. Shiraha;Tatsuya Fujikawa;N. Takaoka;N. Ueda;Y. Nakanishi;K. Koike;A. Takaki;Y. Shiratori

A homosexual Japanese man with acute hepatitis due to hepatitis B virus genotype ae, concurrent with amebic colitis.

一名日本同性恋男子因乙型肝炎病毒 ae 型而患有急性肝炎，并发阿米巴结肠炎。

• 发表时间: 2007
• 期刊: Acta Med Okayama. 61・1
• 作者: Miyake Y;Iwasaki Y;Ishikawa S;Tatsukawa M;Nawa T;Kato J;Takaki A;Kobashi H;Sakaguchi K;Shiratori Y
• 通讯作者: Shiratori Y