Fibrotic Sequelae of Childhood Renal Diseasae

儿童肾病纤维化后遗症

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/8097981
• 关键词: Affect; Angiotensin II; Animals; Arteries; Atherosclerosis; Biological Markers; Blood Vessels; Cells; Cessation of life; Childhood; Chronic; Chronic Kidney Failure; Cicatrix; Diabetic Nephropathy; Dialysis procedure; Equilibrium; Fibrosis; Funding; Genotype; Grant; Hypertension; Inflammatory; Injury; Kidney; Natural Immunity; Patients; Phenotype; Process; Proteomics; Research Personnel; Research Project Grants; Risk; Role; Sclerosis; Structure; Thymosin; Transplantation; Tubular formation; interstitial cell; novel; podocyte; scavenger receptor; toll-like receptor 4

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.

整体中心描述（由申请人提供）： 我们儿科中心拨款的竞争更新将继续关注慢性肾脏病 (CKD) 及其后遗症的各个方面，包括动脉粥样硬化。我们的中心仍然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相同的研究人员领导。第一个项目由 Agnes Fogo 博士领导，研究肾小管间质纤维化的机制，研究新型硬化相关分子胸腺素 (34) 及其抗纤维化代谢物 Ac-SDKP 平衡的净效应。在项目 2 中，博士lekuni Ichikawa 将研究肾损伤后足细胞增殖和分化的潜力，以及对肾脏结构和功能的影响，项目 3 的负责人 Valentina Kon 博士将进行这项研究。由 Allison Eddy 博士领导的项目 4 将继续研究 CKD 中浸润和驻留血管细胞的作用以及加速动脉粥样硬化，以及血管紧张素 II 对这些过程的影响，将研究新型肾小管清道夫受体在肾小管间质纤维化中的作用。及其对炎症细胞募集和由此产生的纤维化的影响 该中心还有三个试点和可行性项目： Charles Alpers 博士将研究先天免疫机制。足细胞，重点关注 Toll 样受体 4 (TLR4) 的作用。 Jamshid Khoshnoodi 博士将使用蛋白质组学方法寻找实验性糖尿病肾病的生物标志物。 Gilbert Moeckel 博士将研究髓质间质细胞中渗透剂积累的机制，以及可能导致纤维化和高血压的后果。 该研究小组汇集了上一个资助周期支持的新观察结果。这个强大的项目组和才华横溢的研究人员，在中心拨款结构提供的协同作用下，将对 CKD 及其后遗症的理解达到新的水平。 相关性：除非采用透析或移植治疗，否则慢性肾脏疤痕会导致死亡。这些研究将研究影响肾小球（肾脏的过滤单位）内的肾小管或称为足细胞的特殊细胞的损伤如何导致疤痕。我们的研究还将探讨慢性肾病患者中出现的动脉硬化（即所谓的动脉粥样硬化）风险大大增加的机制。

项目成果

Galectin-3 preserves renal tubules and modulates extracellular matrix remodeling in progressive fibrosis.

Galectin-3 在进行性纤维化过程中保护肾小管并调节细胞外基质重塑。

• DOI: 10.1152/ajprenal.00326.2010
• 发表时间: 2024-09-14
• 期刊: American journal of physiology. Renal physiology
• 作者: Daryl M. Okamura;Katie Pasichnyk;J. López;Sarah J. Collins;D. Hsu;Fu;A. Eddy
• 通讯作者: A. Eddy

Guarding the kidney architecture: newly recognized physiological role of angiotensin.

保护肾脏结构：新认识的血管紧张素的生理作用。

• DOI: 10.1159/000060160
• 发表时间: 2024-09-14
• 期刊: Contributions to nephrology
• 作者: I. Ichikawa;Y. Miyazaki
• 通讯作者: Y. Miyazaki

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。

• 发表时间: 2000-03-01
• 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

Shigatoxin-1 binding and receptor expression in human kidneys do not change with age.

人类肾脏中的 Shigatoxin-1 结合和受体表达不会随着年龄的增长而改变。

• 发表时间: 2003-03
• 作者: Ergonul, Zuhal;Clayton, Frederic;Fogo, Agnes B;Kohan, Donald E
• 通讯作者: Kohan, Donald E

Pharmacological inhibition and genetic deficiency of plasminogen activator inhibitor-1 attenuates angiotensin II/salt-induced aortic remodeling.

纤溶酶原激活剂抑制剂-1 的药理抑制和遗传缺陷可减弱血管紧张素 II/盐诱导的主动脉重塑。

• 发表时间: 2005-02
• 作者: Weisberg, Alec D;Albornoz, Francisco;Griffin, Jane P;Crandall, David L;Elokdah, Hassan;Fogo, Agnes B;Vaughan, Douglas E;Brown, Nancy J
• 通讯作者: Brown, Nancy J