The effect of simultaneous transfection of HGF gene-plasmid and NFκB-decoy using ultrasound exposure with contrast agent in a rat kidney allograft model

超声造影剂同时转染 HGF 基因质粒和 NFκB 诱饵对大鼠同种异体肾移植模型的影响

• 批准号: 15390499
• 负责人: AZUMA Haruhito
• 金额: $ 4.22万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390499/
• 关键词: NFκB; decoy; Optison; Hepatocyte Growth Factor; kidney transplantation

We have previously demonstrated that in the mechanism of development of chronic allograft nephropathy (CAN), a decreased number of functioning glomeruli due to ischemic-reperfusion injury during renal transplantation as well as acute graft rejection are highly involved ; and activation of nuclear factor kappaB (NFκB) and enhancement of expression of adhesion molecules and cytokine production, mediated by such a factor, constitute important factors in that process. Together with Morishita, Tomita and others, we previously developed "NFκB-decoy", decoy cis-elements oligo deoxyribonucleic acid against NFκB, which modulates expression of inflammatory cytokines and adhesion molecules, and transfected them into kidney transplants in a rat kidney transplantation model for acute rejection using ultrasound exposure with an echocardiographic contrast agent (Gene Ther.2003 Mar ; 10(5):415-25). In the present study, based on the results from our investigation for causes of the failure to induce pe … More rmanent graft survival, we considered the possibility that the renal tubules may directly be impaired by echocardiographic contrast agent, Optison, and ultrasound exposure, and conducted experiments to reduce such adverse effects. In order to induce permanent graft survival by simultaneously suppressing acute graft rejection and tissue damage caused by ultrasound exposure with Optison, as well as reducing ischemic-reperfusion injury during renal transplantation, we developed a plasmid of the gene for hepatocyte growth factor (HGF), which provides protection against renal tubule damage, and transfected it and NFκB-decoy into the donor kidney. (We previously described the inhibitory effect of HGF on renal tubule damage. See Azuma, et al. : J.Am Soc Nephrol ; Tanaka et al. : Am J Transplant.) The present data obtained in the rat kidney transplantation model for acute rejection have shown a significantly prolonged graft survival for animals receiving simultaneous transfection of HGF gene-plasmid and NFκB-decoy, compared with the control transfected with the decoy alone. Unfortunately the treatment failed to induce permanent graft survival, but we will further investigate development of a kidney transplantation method for permanent graft survival. Less

我们以前已经证明，在慢性移植物肾病（CAN）的发展机制中，由于肾移植过程中缺血再灌注损伤以及急性移植物排斥反应导致的功能性肾小球数量减少是高度相关的;以及核因子κ B（NFκB）的活化和粘附分子表达的增强以及由这种因子介导的细胞因子产生，是这一过程中的重要因素。与Morishita、Tomita等人一起，我们先前开发了“NFκB-decoy”，即针对NFκB的诱饵顺式元件寡脱氧核糖核酸，其调节炎性细胞因子和粘附分子的表达，并使用超声心动图造影剂超声暴露将其转染到大鼠肾移植模型中的肾移植物中，以用于急性排斥反应（Gene Ther.2003 Mar ; 10（5）：415-25）。在本研究中，根据我们对未能诱导PE的原因的调查结果， ...更多信息 为了观察移植肾存活率，我们考虑了超声造影剂Optison和超声暴露直接损害肾小管的可能性，并进行了实验以减少此类不良反应。为了通过同时抑制Optison超声照射引起的急性移植物排斥反应和组织损伤，以及减少肾移植过程中的缺血再灌注损伤，诱导移植物永久存活，我们开发了肝细胞生长因子（HGF）基因的质粒，该基因提供对肾小管损伤的保护，并将其和NFκ B-诱饵转染到供体肾中。(We先前描述了HGF对肾小管损伤的抑制作用。参见Azuma等人：J.Am Soc Nephrol ; Tanaka等人：Am J Transplant.）目前在大鼠肾移植急性排斥模型中获得的数据显示，与仅转染诱饵的对照组相比，接受HGF基因-质粒和NFκ B-诱饵同时转染的动物的移植物存活时间显著延长。不幸的是，这种治疗未能诱导移植物永久存活，但我们将进一步研究开发一种肾移植方法，以获得移植物永久存活。少

项目成果

Transfection of NFkappaB-decoy oligodeoxynucleotides using efficient ultrasound-mediated gene transfer into donor kidneys prolonged survival of rat renal allografts.

使用高效超声介导的基因转移将 NFkappaB 诱饵寡脱氧核苷酸转染至供体肾脏中，可延长大鼠肾同种异体移植物的存活时间。

• 发表时间: 2003
• 期刊: Gene Ther 10(5)
• 作者: Morishita R.;Yamasaki K.;Shimamura M.;Ohtani K.;Ahn JD.;Tomita N.;Tomita N.;Morishita R.;Morishita R.;Shimamura M;Yamasaki K;Koike H;Matsumoto K;Tomita N;Namba T;Makino H;Azuma H
• 通讯作者: Azuma H

Cellular localization of GABA and GABAB receptor subunit proteins during spermiogenesis in rat testis

• DOI: 10.2164/jandrol.04185
• 发表时间: 2005-07-01
• 期刊: JOURNAL OF ANDROLOGY
• 作者: Kanbara, K;Okamoto, K;Watanabe, M
• 通讯作者: Watanabe, M

Gamma-aminobutyric acid as a promoting factor of cancer metastasis; induction of matrix metalloproteinase production is potentially its underlying mechanism.

• 发表时间: 2003
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: H. Azuma;T. Inamoto;Takeshi Sakamoto;S. Kiyama;T. Ubai;Y. Shinohara;K. Maemura;M. Tsuji;N. Segawa

Gene therapy with transcription factor decoy oligonucleotides as a potential treatment for cardiovascular diseases.

• DOI: 10.2174/1389450033491055
• 发表时间: 2003-05
• 期刊: Current drug targets
• 影响因子: 3.2
• 作者: N. Tomita;H. Azuma;Y. Kaneda;T. Ogihara;R. Morishita

Epithelial localization of green fluorescent protein-positive cells in epididymis of the GAD67-GFP knock-in mouse

• DOI: 10.2164/jandrol.04157
• 发表时间: 2005-09-01
• 期刊: JOURNAL OF ANDROLOGY
• 作者: Abe, H;Yanagawa, Y;Watanabe, M
• 通讯作者: Watanabe, M