Exploration of new genes related to achivement of transplantation tolerance in living donor liver transplantation

活体肝移植中与移植耐受实现相关的新基因探索

• 批准号: 12307024
• 负责人: UEMOTO Shinji
• 金额: $ 21.58万
• 依托单位: Mie University (2001-2002)Kyoto University (2000)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12307024/
• 关键词: gene; DANmicroarray; living donor liver transplantation; Immunosuppression; transplant tolerance

Seventy recipients were enrolled in elective weaning immunosuppression at Kyoto University Hospital. Twenty-four recipients achieved complete withdrawal of immunosuppression, 37 were during weaning, and 9 encountered rejection. Fifty-four recipients were enrolled in nonelective weaning of immunosuppression. Thirty-four recipients achieved complete withdrawal, 7 were during weaning, and 13 encountered rejection. At Mie University Hospital, 3 recipients were enrolled in nonelective weaning because of EB virus infection. One recipient achieved complete withdrawal, but remaining 2 encountered rejection.Total RNA was extracted from peripheral blood lymphocytes of recipients who accomplished complete withdrawal of immunosuppression and normal volunteers. RNA was analyzed by cDNA microarray (Agilent) comparing mRNA expression of recipients with that of normal volunteers. Number of genes with up-regulated mRNA expression was 120, and that with down-regulated expression was 169. Genes with up-regulated or down-regulated expression were divided into subgroups according to gene-related function. Number of up-regulated or down-regulated genes were 4/3 for [Apoptosis], 2/2 for [Cell cycle], 2/7 for [Cytokine], 4/4 for [DNA metabolism], 1/0 for [Heat shock protein], 3/7 for [Receptor], 16/18 for [Signal transduction], 7/14 for [Stress], 8/13 for [Transcription], 9/14 for [Transporter], and 72/113 for undetermined factor, respectively.

在京都大学医院，70名接受者参加了选择性断奶免疫抑制。24名受者达到完全撤销免疫抑制，37人在断奶期间，9人遇到排斥反应。54名受者参加了非选择性撤机免疫抑制。34例受体完全退出，7例处于断奶期，13例发生排斥反应。在三重大学医院，3名受者因EB病毒感染而入选非选择性断奶。从完全撤除免疫抑制的受者和正常志愿者外周血淋巴细胞中提取总RNA。通过cDNA微阵列（Agilent）分析RNA，比较受体与正常志愿者的mRNA表达。mRNA表达上调的基因有120个，表达下调的基因有169个。根据基因相关功能将表达上调或下调的基因分为亚组。上调或下调的基因数量分别为：[凋亡] 4/3，[细胞周期] 2/2，[细胞因子] 2/7，[DNA代谢] 4/4，[热休克蛋白] 1/0，[受体] 3/7，[信号转导] 16/18，[应激] 7/14，[转录] 8/13，[转运蛋白] 9/14，待定因素为72/113。

项目成果

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L郭等人：“使用抗诱导共刺激剂（ICOS）的小鼠单克隆抗体延长大鼠肝移植的存活率”移植。

X-K.Li, et.al: "Fulminant Hepatitis by Fas-Ligand Expression in MRL-lpr/lpr Mice Grafted with Fas-Positive Livers and Wild-Type Mice with Fas-Mutant Livers."Transplantation. (in press).

X-K.Li 等人：“移植有 Fas 阳性肝脏的 MRL-lpr/lpr 小鼠和移植有 Fas 突变肝脏的野生型小鼠中 Fas 配体表达引起的暴发性肝炎。”移植。

M.Ohba, XK.Li, Y.Kita, S.Enosawa, N.Funeshima, H.Nagai, HQ.Zhang, et al.: "Long-term graft acceptance in rat heart transplantation by CLTA4Ig gene transfection combined with FTY720 treatment"World J Surg. 25・4. 391-398 (2001)

M.Ohba、XK.Li、Y.Kita、S.Enosawa、N.Funeshima、H.Nagai、HQ.Zhang 等：“CLTA4Ig 基因转染联合 FTY720 治疗在大鼠心脏移植中的长期移植接受《世界外科杂志》25・4.391-398（2001）

X-K.Li, et.al: "Induction of lymphocyte apoptosis in rat liver allograft with ongoing rejection by FTY720."Clinical and Experimental Immunology. 123(2). 331-339 (2001)

X-K.Li 等人：“FTY720 持续排斥大鼠肝同种异体移植物中淋巴细胞凋亡的诱导”。临床和实验免疫学。

高槻光寿: "生体肝移植後の免疫抑制剤減量・離脱の試み"今日の移植. 13・1. 19-23 (2000)

Mitsutoshi Takatsuki：“活体肝移植后尝试减少或停用免疫抑制剂”，《今日移植》13・1（2000）。