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
- 来源:
- 关键词:AddressAdultAnimal ModelAnti-Inflammatory AgentsAnti-inflammatoryApplications GrantsAttenuatedBehaviorBlood PressureBlood VesselsBody FluidsCell AgingCellsDataDefectDevelopmentDiseaseEnsureExcretory functionFaceFailureFibroblast Growth Factor 2FibrosisFluid BalanceFunctional disorderGenerationsGenetic ProgrammingGlomerulonephritisHomeostasisHypertensionImpairmentInflammationInflammatoryInjuryKidneyKidney DiseasesLeadMaintenanceMediatingMolecularNormal CellOrganPathogenesisPlayRattusRegulationRenal functionReportingResourcesRoleSignal TransductionSodiumSodium ChlorideSprague-Dawley RatsStem cellsTestingTubular formationWorkbasecell behaviorhypoxia inducible factor 1improvedin vivoinsightinterstitialkidney cellkidney medullanormotensivenovel therapeuticsrepairedresponsesalt intakesalt sensitiveself-renewalstemstem cell biologystem cell differentiationstem cell niche
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.
干细胞驻留在体内的特殊微环境被称为干细胞利基,这是
通过提供外源性调节因子,对干细胞的维持、自我更新和分化至关重要。
肾髓质最近被认为是成人肾干细胞和这些肾髓质的利基。
干细胞在肾髓质的正常结构和功能维持中起着重要作用。它
众所周知,肾髓质在钠排泄调节中起着重要作用,而且
肾髓质功能障碍与盐敏感型高血压有关。我们想知道茎是不是
肾髓质中的细胞龛,通过调节干细胞的行为,有助于维持
肾脏区域的正常功能完整性,从而对动脉血压的长期控制,
以及盐敏感型高血压是否与脑内干细胞资源或生态位受损有关
肾髓质。在初步研究中,我们发现一种重要的干细胞利基因子,成纤维细胞的水平
观察大鼠骨髓细胞生长因子-2(FGF2)、CD133阳性干细胞数量及对高盐摄入量的反应
Dahl盐敏感型高血压大鼠(Dahl S)肾髓质明显减少
血压正常的大鼠。研究还发现,FGF2水平的降低与
低氧诱导因子(HIF)-1和干细胞巢功能改善可减少促炎作用
达尔-S大鼠肾髓质因子与盐敏感性高血压的关系。这些数据表明,
干细胞巢的缺陷可能导致干细胞的异常生成、动员和分化。
从而导致肾髓质结构和功能完整性的维持失败
面对高盐的挑战,最终导致Dahl-S大鼠的盐敏性高血压。基于这些
结果,我们假设肾髓质干细胞巢在肾脏的调节中起着关键作用。
骨髓功能和干细胞巢缺陷在高血压发病中的作用
达尔·S大鼠。为了验证这一假设,我们将首先确定FGF2对干细胞行为的调节是否在
肾髓质对肾髓质功能的调节以及该干细胞的缺陷是否
生态位因子在Dahl-S大鼠盐敏感型高血压发病中的作用然后我们将探索
Dahl-S大鼠肾髓质干细胞巢缺陷的机制
HIF-1受损和随之而来的成纤维细胞生长因子-2水平降低是否是导致这一缺陷的原因
骨髓干细胞壁龛。最后,我们将确定肾骨髓干细胞巢的缺陷是如何
DAHL-S大鼠肾髓质功能障碍及高血压,主干不足
肾髓质中细胞介导的抗炎作用。这些拟议研究的结果将
明确一个重要的细胞/分子机制,介导肾脏髓质对高盐摄入量的适应
为盐敏感型高血压的干细胞相关发病机制提供新的见解。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Ningjun Li其他文献
Ningjun Li的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 35.58万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 35.58万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 35.58万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 35.58万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 35.58万 - 项目类别:
Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 35.58万 - 项目类别:
Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
- 批准号:
10065645 - 财政年份:2023
- 资助金额:
$ 35.58万 - 项目类别:
Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 35.58万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 35.58万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 35.58万 - 项目类别:
Grant-in-Aid for Scientific Research (C)














{{item.name}}会员




