Therapetic strategy for chronic hepatitis C by inducing apoptosis of hepatocyte infected with hepatitis C virus

诱导丙型肝炎病毒感染肝细胞凋亡治疗慢性丙型肝炎的治疗策略

• 批准号: 11470132
• 负责人: HAYASHI Norio
• 金额: $ 9.02万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470132/
• 关键词: Hepatitis C virus; Apoptosis; Cell cycle; Hepatocyte; Core; Microarray; 樹状細胞; IL-12; 抗アポト-シス

To investigate influence of hepatitis C virus (HCV) infection on hepatocyte, we established several permanent hepatocyte clones that express HCV core gene. Microarray analysis of these clones revealed a couple of gene of which expression was modulated in HCV core-expressing clones. We applied Nothern blot analysis to confirm 2 genes of which expression was downrgulated as well as 3 genes of which expression was upregulated in HCV core-expressing clones. We are currently analyzing the role of these genes in hepatocytes. We also investigated the effect of HCV core expression on apoptosis as well as cell proliferation. Expression of HCV core gene did not affect apoptosis, but significantly retarded proliferation of hepatocyte by inhibiting G1/S transition. These results suggest that infection of HCV inhibits hepatocyte proliferation but does not affect apoptosis of hepatocytes, raising the possibility that HCV-infected hepatocytes can be eradicated by apoptotic stimuli.

为研究丙型肝炎病毒（HCV）感染对肝细胞的影响，我们建立了几个表达HCV核心基因的永久性肝细胞克隆。这些克隆的微阵列分析揭示了一对夫妇的基因表达的HCV核心表达克隆调制。我们应用Nothern印迹分析来确认在HCV核心表达克隆中表达下调的2个基因以及表达上调的3个基因。我们目前正在分析这些基因在肝细胞中的作用。我们还研究了HCV核心表达对细胞凋亡和细胞增殖的影响。HCV核心基因的表达不影响细胞凋亡，但通过抑制G1/S转换而显著抑制肝细胞增殖。这些结果表明，HCV感染抑制肝细胞增殖，但不影响肝细胞凋亡，提高了HCV感染的肝细胞可以通过凋亡刺激根除的可能性。

项目成果

Ishida H, et al.: "Identification of multiple transcription factors, HLF, FTF, and E4BP4, controlling hepatitis B virus enhancer."J Virol. 74. 1241-1251 (2000)

Ishida H 等人：“控制乙型肝炎病毒增强子的多种转录因子 HLF、FTF 和 E4BP4 的鉴定。”J Virol。

Tanaka Y, et al.: "Probability of hepatocellular carcinoma of small hepatocellular nodules undetectable bu computed tomography during arterial portography."Hepatology. 31. 890-898 (2000)

Tanaka Y 等人：“动脉门静脉造影期间计算机断层扫描无法检测到小肝细胞结节的肝细胞癌的可能性。”肝病学。

Tanaka Y, Sasaki Y, Katayama K, Hiramatsu N, Ito A, Murata H, Enomoto N, Oshita M, Mochizuki K, Ysujii M, Tsuji S, Kasahara A, Tomoda K, Nakamura H, Hayashi N, Hori M.: "Probability of hepatocellular carcinoma of small hepatocellular nodules undetectable

田中 Y、佐佐木 Y、片山 K、平松 N、伊藤 A、村田 H、榎本 N、大下 M、望月 K、Ysujii M、辻 S、笠原 A、友田 K、中村 H、林 N、堀 M："

Ishida H, Ueda K, Ohkawa K, Kanazawa Y, Hosui A, Nakanishi F, Mita E, Kasahara A, Sasaki Y, Hori M, Hayashi N.: "Identification of multiple transcription factors, HLF, FTF, and E4BP4, controlling hepatitis B virus enhancer II"J Virol. 74. 1241-1251 (2000)

Ishida H、Ueda K、Ohkawa K、Kanazawa Y、Hosui A、Nakanishi F、Mita E、Kasahara A、Sasaki Y、Hori M、Hayashi N.：“多种转录因子 HLF、FTF 和 E4BP4 的鉴定，控制肝炎

Yamamoto M.: "Intarcellular single-chain antibody against hepatitis B virus cultured cells"Hepatology. 30. 300-307 (1999)

Yamamoto M.：“抗乙型肝炎病毒培养细胞的细胞内单链抗体”肝病学。