Pathology of the FSGS Kidney
FSGS 肾脏的病理学
基本信息
- 批准号:7613972
- 负责人:
- 金额:$ 35.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-30 至 2011-09-29
- 项目状态:已结题
- 来源:
- 关键词:ApoptoticArtsAttentionBiopsyCell Culture TechniquesCell CycleCell DeathCell Differentiation processCellsChildCicatrixClinicalDiseaseDystroglycanElementsEpithelial CellsExperimental ModelsExtracellular MatrixFibrosisFocal Segmental GlomerulosclerosisFunctional disorderFutureGelatinase AGelatinase BGenomicsHealthHilarHistologicHumanIn Situ Nick-End LabelingInfiltrationInflammatoryInjuryKidneyLesionMediator of activation proteinMesenchymalMessenger RNAMetalloproteasesMolecularMulticenter StudiesMyofibroblastNPHS2 proteinNational Institute of Diabetes and Digestive and Kidney DiseasesNatureOutcomePathologyPathway interactionsPatientsPatternPhenotypePlasminogen Activator Inhibitor 1PlayProcessPrognostic MarkerProteinsProteomicsRandomized Controlled TrialsRoleSclerosisSpecimenTestingTherapeuticTissuesTransforming Growth FactorsTubular formationcase controlcell behaviorcell typecomputerizedinflammatory modulationinhibitor/antagonistinterstitialinterstitial cellmacrophagemesangial cellnephrinnew therapeutic targetpodocyteprognosticpromoterprospectiveresponseresponse to injurysynaptopodintranslational studyyoung adult
项目摘要
DESCRIPTION (provided by applicant): While considerable progress has been achieved in understanding basic mechanisms of glomerular and renal fibrosis, the absence of a true experimental model for human FSGS has made it difficult to clearly understand how these basic mechanisms apply to human idiopathic FSGS. A second major limitation has been that mesenchymal cells such as mesangial cells and interstitial cells and tubular epithelial cells have received the most attention in defining pathways of sclerosis and fibrosis, while a less well studied cell, the podocyte, plays a major role in the injuries leading to FSGS. Recently, the NIDDK initiated a prospective, controlled, randomized trial to study the treatment of FSGS in children and young adults. Our studies aim to perform state-of-the art analysis of the renal biopsy tissue obtained for patient entry into this multicenter study, along with additional cases from our archival files, with a total of >2000 cases, with >200 in children. We will analyze histologic patterns of injury and correlate them with expression by specific glomerular cell types of protein and mRNA of mediators of cell differentiation, proliferation, ECM modulation and inflammatory modulators. These approaches will take advantage of the highly localized injuries in FSGS, i.e. the focal and segmental nature of the sclerosing lesions. Colocalization of mediators with expressions of candidate modulators of the disease process, as proposed in this project, is the first essential step in fulfilling Koch's postulates for establishing a causal role in disease, which can then be explored in complementary studies, e.g. cell culture, proteomic, genomic analyses in future studies. A key element will be the correlation of renal biopsy tissue findings with clinical outcome, to determine markers of prognosis and therapeutic response. These translational studies will utilize findings from the clinical specimens to provide an initial test of the putative pathogenetic roles of the leading molecular "suspects" that result in FSGS. These approaches could ultimately identify novel therapeutic targets in FSGS.
描述(由申请人提供):虽然在理解肾小球和肾纤维化的基本机制方面取得了很大的进步,但缺乏人类FSG的真实实验模型,使得很难清楚地了解这些基本机制如何应用于人类特发性FSG。第二个主要局限性是间充质细胞(例如肾小球细胞,间质细胞和管状上皮细胞)在定义硬化和纤维化途径方面受到最大的关注,而细胞较少的细胞(Podocyte)在导致FSGS的损伤中起着主要作用。最近,NIDDK发起了一项前瞻性,受控的随机试验,研究儿童和年轻人的FSG治疗。我们的研究旨在对患者进入这项多中心研究的肾脏活检组织进行最新分析,以及我们的档案文件中的其他病例,总共> 2000例,儿童> 200。我们将通过特定的细胞分化,增殖,ECM调节和炎症调节剂的蛋白质和mRNA的特定肾小球细胞类型和mRNA来分析损伤的组织学模式。这些方法将利用FSG中高度局部的伤害,即硬化病变的焦点和分段性质。正如本项目中提出的那样,与疾病过程的候选调节剂表达的调解人共定位是实现科赫假设在疾病中建立因果作用的第一步,然后可以在互补研究中探索。未来研究中的细胞培养,蛋白质组学,基因组分析。一个关键要素将是肾脏活检组织发现与临床结果的相关性,以确定预后和治疗反应的标志。这些翻译研究将利用临床标本中的发现,对导致FSG的主要分子“可疑”的假定致病作用提供初步测试。这些方法最终可以鉴定出FSG中的新型治疗靶标。
项目成果
期刊论文数量(0)
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AGNES B. FOGO其他文献
AGNES B. FOGO的其他文献
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{{ truncateString('AGNES B. FOGO', 18)}}的其他基金
Vanderbilt O'Brien Kidney Center-Core B Histology and Molecular Pathology Core
范德比尔特奥布莱恩肾脏中心-核心 B 组织学和分子病理学核心
- 批准号:
10163167 - 财政年份:2017
- 资助金额:
$ 35.01万 - 项目类别:
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相似海外基金
2010 Glycolipid & Sphingolipid Biology Gordon Research Conference
2010糖脂
- 批准号:
7800051 - 财政年份:2009
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