Fibrotic Sequelae of Childhood Renal Diseasae

儿童肾病纤维化后遗症

基本信息

批准号：
8097981
负责人：
AGNES B. FOGO
金额：
$ 93.45万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-05-01 至 2013-05-31
项目状态：
已结题

项目摘要

DESCRIPTION, OVERALL CENTER (provided by applicant): This competing renewal of our pediatric center grant will continue to focus on varying aspects of chronic kidney disease (CKD), and its sequelae, including atherosclerosis. Our Center continues to be composed of four original research projects and two cores (an administrative core, and an animal phenotyping and genotyping core), all led by the same investigators as for the last submission. The first project, led by Dr. Agnes Fogo, examines mechanisms of tubulointerstitial fibrosis, investigating the net effect of the balance of the novel sclerosis-associated molecule thymosin (34 and its anti-fibrotic metabolite, Ac-SDKP. In project 2, Dr. lekuni Ichikawa will examine the potential of podocyte proliferation and differentiation after renal injury, and the effects on renal structure and function. Dr. Valentina Kon, leading Project 3, will continue study of the role of infiltrating and resident vascular cells and accelerated atherosclerosis in CKD, and effects of angiotensin II on these processes. Project 4, led by Dr. Allison Eddy, will examine the role of novel renal tubular scavenger receptors in tubulointerstitial fibrosis, and their impact on inflammatory cell recruitment and resulting fibrosis. The Center also has three pilot and feasibility projects: Dr. Charles Alpers will examine mechanisms of innate immunity of the podocyte, focusing on the role of toll-like receptor 4 (TLR4). Dr. Jamshid Khoshnoodi will search for biomarkers of experimental diabetic nephropathy using a proteomic approach. Dr. Gilbert Moeckel will examine mechanisms of osmolyte accumulation in medullary interstitial cells, with possible consequences for fibrosis and hypertension. This team of investigators brings together novel observations supported by the last funding cycle. This strong group of projects and talented investigators, with the synergy provided by the center grant structure, will achieve a new level of understanding of CKD and its sequelae. Relevance: Chronic kidney scarring results in death unless treated with dialysis of transplantation. These studies will examine how injuries that affects the tubules or specialized cells called podocytes within the glomeruli (the filtering units of the kidney) result in scarring. Our studies will also examine the mechanisms of the greatly increased risk of hardening of the arteries, so-called atherosclerosis, that is seen in patients with chronic kidney disease.

描述，整体中心（由申请人提供）：我们儿科中心赠款的这种竞争续约将继续关注慢性肾脏疾病（CKD）及其后遗症的各个方面，包括动脉粥样硬化。我们的中心继续由四个原始研究项目和两个核心（一个行政核心，一个动物表型和基因分型核心）组成，所有这些都由与上次提交的研究人员一起领导。由Agnes Fogo博士领导的第一个项目检查了肾小管间质纤维化的机制，研究了新型硬化症相关的分子胸腺素的平衡的净效应（34及其抗纤维化代谢物，AC-SDKP，项目2中的AC-SDKP。项目2中的AC-SDKP。结构和功能。纤维化。 Toll样受体4（TLR4）的作用。 Jamshid Khoshnoodi博士将使用蛋白质组学方法搜索实验性糖尿病性肾病的生物标志物。吉尔伯特·莫克尔（Gilbert Moeckel）博士将检查髓质间质细胞中渗透液积累的机制，对纤维化和高血压产生可能的影响。这支调查人员团队汇集了在上一个融资周期支持的新颖观察结果。这一强大的项目和才华横溢的调查人员以及中心赠款结构提供的协同作用将对CKD及其后遗症提高新水平。相关性：慢性肾脏疤痕会导致死亡，除非接受移植的透析治疗。这些研究将研究影响肾小球内称为足细胞的小管或专门细胞的损伤如何导致疤痕。我们的研究还将研究大大增加动脉硬化风险的机制，即所谓的动脉粥样硬化，这在患有慢性肾脏疾病的患者中可以看到。

项目成果

期刊论文数量（114）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Oxidants induce transcriptional activation of manganese superoxide dismutase in glomerular cells.

DOI：
10.1038/ki.1994.288
发表时间：
1994-08
期刊：
Kidney international
影响因子：
19.6
作者：
T. Yoshioka;T. Homma;B. Meyrick;M. Takeda;T. Moore-Jarrett;V. Kon;I. Ichikawa
通讯作者：
T. Yoshioka;T. Homma;B. Meyrick;M. Takeda;T. Moore-Jarrett;V. Kon;I. Ichikawa

Dual renin gene targeting by Cre-mediated interchromosomal recombination.

通过 Cre 介导的染色体间重组实现双重肾素基因靶向。

DOI：
10.1006/geno.2000.6113
发表时间：
2000
期刊：
Genomics.
影响因子：
0
作者：
Matsusaka,T;Kon,V;Takaya,J;Katori,H;Chen,X;Miyazaki,J;Homma,T;Fogo,A;Ichikawa,I
通讯作者：
Ichikawa,I

HDAC inhibitors regulate claudin-1 expression in colon cancer cells through modulation of mRNA stability.

DOI：
10.1038/onc.2009.324
发表时间：
2010-01-14
期刊：
ONCOGENE
影响因子：
8
作者：
Krishnan, M.;Singh, A. B.;Smith, J. J.;Sharma, A.;Chen, X.;Eschrich, S.;Yeatman, T. J.;Beauchamp, R. D.;Dhawan, P.
通讯作者：
Dhawan, P.

Angiotensin receptor blocker protection against podocyte-induced sclerosis is podocyte angiotensin II type 1 receptor-independent.

DOI：
10.1161/hypertensionaha.109.141994
发表时间：
2010-04
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
0
作者：
Matsusaka T;Asano T;Niimura F;Kinomura M;Shimizu A;Shintani A;Pastan I;Fogo AB;Ichikawa I
通讯作者：
Ichikawa I

Mitogenic signaling of urokinase receptor-deficient kidney fibroblasts: actions of an alternative urokinase receptor and LDL receptor-related protein.

尿激酶受体缺陷的肾成纤维细胞的有丝分裂信号传导：另一种尿激酶受体和低密度脂蛋白受体相关蛋白的作用。