Renal Medullary Stem Cell Niche in Salt Sensitive Hypertension

盐敏感性高血压中的肾髓质干细胞生态位

基本信息

  • 批准号:
    8386965
  • 负责人:
  • 金额:
    $ 35.58万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-01-01 至 2014-11-30
  • 项目状态:
    已结题

项目摘要

The specialized microenvironment where the stem cells reside in vivo is termed stem cell niche, which is critical for the maintenance, self-renewal and differentiation of stem cells by providing extrinsic regulators. Renal medulla has recently been identified as a niche for adult kidney stem cells and these renal medullary stem cells are importantly involved in the normal structural and functional maintenance in the renal medulla. It is well known that the renal medulla plays an important role in the regulation of sodium excretion and that dysfunctions in the renal medulla are involved in salt-sensitive hypertension. We wondered whether the stem cell niche in the renal medulla, through regulating the behavior of stem cells, contributes to the maintenance of normal functional integrity in this kidney region and thereby to the long-term control of arterial blood pressure, and whether salt-sensitive hypertension is associated with the impairment of stem cell resource or niche in the renal medulla. In preliminary studies, we found that the level of an important stem cell niche factor, fibroblast growth factor-2 (FGF2), the number of CD133 positive stem cells and their responses to high salt intake were significantly decreased in the renal medulla in Dahl salt-sensitive hypertensive (Dahl S) rats compared with normotensive rats. It was also found that the decreased FGF2 level was associated with a deficiency in hypoxia-inducible factor (HIF)-1¿ and that improving stem cell niche function decreased pro-inflammatory factors in the renal medulla and attenuated salt-sensitive hypertension in Dahl S rats. These data indicate that a defect of stem cell niche may lead to abnormal generation, mobilization and differentiation of stem cells in the renal medulla and thereby lead to a failure of maintenance of renal medullary structural and functional integrity in face to high salt challenge, ultimately resulting in salt-sensitive hypertension in Dahl S rats. Based on these findings, we hypothesize that the renal medullary stem cell niche plays a critical role in the regulation of renal medullary function and the defect of such stem cell niche contributes to the development of hypertension in Dahl S rats. To test this hypothesis, we will first determine whether FGF2 regulation of stem cell behavior in the renal medulla contributes to the regulation of renal medullary function and whether a defect of this stem cell niche factor mediates the development of salt-sensitive hypertension in Dahl S rats. We will then explore the mechanisms causing the defect of the stem cell niche in the renal medulla of Dahl S rats by determining whether impaired HIF-1¿ and consequent decreases in FGF-2 levels contribute to the deficiency of this medullary stem cell niche. Finally, we will determine how the defect of renal medullary stem cell niche produces renal medullary dysfunction and hypertension in Dahl S rats, focusing on the insufficiency of stem cell-mediated anti-inflammatory actions in the renal medulla. The results from these proposed studies will define an important cellular/molecular mechanism mediating renal medullary adaptation to high salt intake and provide new insights into the stem cell-associated pathogenesis of salt-sensitive hypertension.
干细胞在体内生存的特殊微环境被称为干细胞生态位

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Ningjun Li其他文献

Ningjun Li的其他文献

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{{ truncateString('Ningjun Li', 18)}}的其他基金

Inhibition of fatty acid amide hydrolase as a novel strategy to prevent nephrotoxicity of cisplatin.
抑制脂肪酸酰胺水解酶作为预防顺铂肾毒性的新策略。
  • 批准号:
    10684803
  • 财政年份:
    2022
  • 资助金额:
    $ 35.58万
  • 项目类别:
Inhibition of fatty acid amide hydrolase as a novel strategy to prevent nephrotoxicity of cisplatin.
抑制脂肪酸酰胺水解酶作为预防顺铂肾毒性的新策略。
  • 批准号:
    10513011
  • 财政年份:
    2022
  • 资助金额:
    $ 35.58万
  • 项目类别:
Renal sphingosine-1-phosphate receptor 1 in salt-sensitive hypertension
盐敏感性高血压中的肾 1-磷酸鞘氨醇受体 1
  • 批准号:
    10319594
  • 财政年份:
    2019
  • 资助金额:
    $ 35.58万
  • 项目类别:
Renal sphingosine-1-phosphate receptor 1 in salt-sensitive hypertension
盐敏感性高血压中的肾 1-磷酸鞘氨醇受体 1
  • 批准号:
    10064007
  • 财政年份:
    2019
  • 资助金额:
    $ 35.58万
  • 项目类别:
Molecular mechanism of hypertension-induced renal injury: the role of HIF-1alpha
高血压肾损伤的分子机制:HIF-1α的作用
  • 批准号:
    9383995
  • 财政年份:
    2017
  • 资助金额:
    $ 35.58万
  • 项目类别:
Renal Medullary Stem Cell Niche in Salt Sensitive Hypertension
盐敏感性高血压中的肾髓质干细胞生态位
  • 批准号:
    8207205
  • 财政年份:
    2011
  • 资助金额:
    $ 35.58万
  • 项目类别:
Renal Medullary Stem Cell Niche in Salt Sensitive Hypertension
盐敏感性高血压中的肾髓质干细胞生态位
  • 批准号:
    8024001
  • 财政年份:
    2011
  • 资助金额:
    $ 35.58万
  • 项目类别:
Renal Medullary Stem Cell Niche in Salt Sensitive Hypertension
盐敏感性高血压中的肾髓质干细胞生态位
  • 批准号:
    8584315
  • 财政年份:
    2011
  • 资助金额:
    $ 35.58万
  • 项目类别:
Renal medullary HIF prolyl hydroxylases and salt sensitivity of blood pressure
肾髓质HIF脯氨酰羟化酶与血压盐敏感性
  • 批准号:
    7841255
  • 财政年份:
    2009
  • 资助金额:
    $ 35.58万
  • 项目类别:
Renal medullary HIF prolyl hydroxylases and salt sensitivity of blood pressure
肾髓质HIF脯氨酰羟化酶与血压盐敏感性
  • 批准号:
    7481007
  • 财政年份:
    2007
  • 资助金额:
    $ 35.58万
  • 项目类别:

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