suPAR and renal fibrosis

suPAR与肾纤维化

基本信息

  • 批准号:
    10220027
  • 负责人:
  • 金额:
    $ 45.04万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-07-20 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

Abstract Chronic kidney disease (CKD) is a major driver of mortality and a financial challenge for healthcare in the United States. Treatment options are scarce, indirect and not sufficient, whilst CKD is growing into one of the largest unmet medical needs of our time. Once the kidney is injured, progression of the disease is dependent on the degree of fibrosis, which can differ from patient to patient. We and others have made the unique observation that the soluble form of urokinase plasminogen activator receptor (uPAR) is a risk factor for incident and prevalent kidney diseases across the spectrum of CKD. suPAR is a three finger toxin that is produced by immature myeloid cells in the bone marrow and circulates in the plasma to regulate integrin function in the kidney. Elevated suPAR levels or the presence of certain suPAR isoforms are causally involved in CKD by mediating injury to both glomerular podocytes and proximal tubular cells through specific interactions with β integrins. Building on our published and novel preliminary observations that suPAR-mediated integrin activation drives fibrotic programs in the kidney, we plan to investigate the consequences of suPAR interactions with distinct β integrins in different nephron segments and explore its role in promoting both glomerular and tubulointerstitial fibrosis. Three independent aims are being proposed: First, we will determine the molecular mechanisms that translate suPAR-αvβ3 integrin signaling into podocyte injuries and glomerular sclerosis using surface plasmon resonance assays, cultured cell experiments and suPAR transgenic mouse models. Second, we will determine the molecular mechanisms that drive suPAR-αvβ6 integrin signaling in tubular injuries and tubulointerstitial fibrosis by genetically modifying the tubular integrin function. Third, we will investigate therapeutic modalities using peptide based blocking strategies for uPAR and its associated fibrotic pathways. Experiments outlined in this proposal will allow us to separate different steps in the suPAR cascade of kidney fibrosis and define best options to intervene. As such, insights from this grant will provide a basis for preventive and treatment strategies to combat suPAR mediated fibrosis and CKD.
摘要

项目成果

期刊论文数量(0)
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会议论文数量(0)
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Jochen Reiser其他文献

Jochen Reiser的其他文献

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{{ truncateString('Jochen Reiser', 18)}}的其他基金

Role of proteolytic suPAR fragment in insulin dependent diabetes and kidney disease
蛋白水解suPAR片段在胰岛素依赖性糖尿病和肾脏疾病中的作用
  • 批准号:
    10654224
  • 财政年份:
    2023
  • 资助金额:
    $ 45.04万
  • 项目类别:
suPAR and renal fibrosis
suPAR与肾纤维化
  • 批准号:
    10412048
  • 财政年份:
    2020
  • 资助金额:
    $ 45.04万
  • 项目类别:
suPAR and renal fibrosis
suPAR与肾纤维化
  • 批准号:
    10035085
  • 财政年份:
    2020
  • 资助金额:
    $ 45.04万
  • 项目类别:
suPAR and renal fibrosis
suPAR与肾纤维化
  • 批准号:
    10620226
  • 财政年份:
    2020
  • 资助金额:
    $ 45.04万
  • 项目类别:
The KIDCOV Study: Assessment of Kidney Injury and Associated Risk Factors for SARS-CoV-2
KIDCOV 研究:评估 SARS-CoV-2 肾损伤及相关风险因素
  • 批准号:
    10216618
  • 财政年份:
    2017
  • 资助金额:
    $ 45.04万
  • 项目类别:
CD40 autoantibody and FSGS recurrence
CD40自身抗体与FSGS复发
  • 批准号:
    9912137
  • 财政年份:
    2017
  • 资助金额:
    $ 45.04万
  • 项目类别:
CD40 autoantibody and FSGS recurrence
CD40自身抗体与FSGS复发
  • 批准号:
    9333947
  • 财政年份:
    2017
  • 资助金额:
    $ 45.04万
  • 项目类别:
A Humanized Mouse Model of FSGS
FSGS 人源化小鼠模型
  • 批准号:
    9070608
  • 财政年份:
    2015
  • 资助金额:
    $ 45.04万
  • 项目类别:
Role of Circulating suPAR in FSGS
循环 suPAR 在 FSGS 中的作用
  • 批准号:
    8882417
  • 财政年份:
    2013
  • 资助金额:
    $ 45.04万
  • 项目类别:
Role of Circulating suPAR in FSGS
循环 suPAR 在 FSGS 中的作用
  • 批准号:
    8735143
  • 财政年份:
    2013
  • 资助金额:
    $ 45.04万
  • 项目类别:

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