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

基本信息

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

项目摘要

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

我们先前已经证明，在慢性同种异体移植肾病（CAN）的发育机理中，由于肾移植期间缺血性 - 重新灌注损伤以及急性移植的抑制作用而导致的肾小球功能降低。核因子Kappab（NFκB）的激活以及通过这种因子介导的粘合分子和细胞因子产生的表达增强，构成了该过程的重要因素。我们先前与Morishita，Tomita等人一起开发了“NFκB-Decoy”，诱饵顺式元素寡核酸氧化核酸与NFκB，该核酸对NFκB进行了调节，该核酸调节了炎症细胞因子和粘合分子的表达，并使用它们在肾脏挤出型肾脏中的肾脏置换术中转移到肾脏中，并将其转移到肾小管上的脉冲模型中。（Gene Ther.2003 Mar; 10（5）：415-25）。在本研究中，基于我们调查的结果，该研究的原因是未能诱导PE的原因……更多的移植物存活率，我们认为肾小管可能会直接受到超声心动造影剂，OPTISON和超声暴露的可能性，并进行了实验，以减少这种不良影响。为了通过简单地抑制Optison超声暴露而引起的急性移植排斥和组织损害来诱导永久的移植生存，并减少肾移植期间的缺血性 - 再灌注损伤，我们开发了肝细胞生长因子（HGF（HGF）基因的质粒（HGF），该基因为肾脏损害提供了保护和NF的保护和NF。 (We previously described the inhibitory effect of HGF on renal tuber damage. See Azure, 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 transformation of HGF gene-plasmid and NFκB-decoy, compared with the control单独翻译成诱饵。不幸的是，这种处理未能诱导永久性移植物存活，但我们将进一步研究肾脏移植方法的永久移植生存方法。较少的

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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。

DOI：
发表时间：
2003
期刊：
Gene Ther 10(5)
影响因子：
0
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
影响因子：
0
作者：
Kanbara, K;Okamoto, K;Watanabe, M
通讯作者：
Watanabe, M

Significant prolongation of animal survival by combined therapy of FR167653 and cyclosporine A in rat renal allografts.

FR167653 和环孢素 A 联合治疗大鼠同种异体肾移植物可显着延长动物存活时间。

DOI：
发表时间：
2003
期刊：
Transplantation. 76・7
影响因子：
0
作者：
Azuma H;Wada T;Gotoh R;Furuichi K;Sakai N;Yazawa K;Yokoyama H;Katsuoka Y;Takahara S.
通讯作者：
Takahara S.

Involvement of angiopoietins in cancer progression in association with cancer cell-- fibro blast interaction.

血管生成素参与癌症进展与癌细胞-成纤维细胞相互作用相关。