Adipose-derived sPRR controls circadian rhythm of blood pressure through inhibition of renal NCC activity

脂肪源性 sPRR 通过抑制肾 NCC 活性来控制血压的昼夜节律

基本信息

  • 批准号:
    10522511
  • 负责人:
  • 金额:
    $ 63.07万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-07-01 至 2026-06-30
  • 项目状态:
    未结题

项目摘要

Summary Blood pressure (BP) and renal Na+ excretion exhibit diurnal rhythms and dysregulation of these rhythms leads to nocturnal hypertension, a strong predictor of cardiovascular disease and target organ damage. Multiple Na+ transporters along the nephron are under the control of circadian regulation. In particular, renal abundance of phosphorylated NaCl cotransporter (p-NCC), a surrogate marker of activated NCC, exhibits robust rhythmicity in the kidney whereas total NCC (t-NCC) abundance remains constant. Disruption of p-NCC rhythmicity is associated with impaired circadian rhythm of BP. Preliminary results showed that adipose- derived soluble (pro)rein receptor (sPRR) functions as a key regulator of circadian rhythm of BP via angiotensin type 2 receptor (AT2R)-dependent dephosphorylation of NCC. In this regard, adipose-specific deletion of PRR or its upstream regulator PPARγ remarkably suppressed circadian rhythms of BP accompanied with suppressed release of soluble PRR (sPRR). The circadian phenotype was recapitulated by mutagenesis of the cleavage site of PRR. Supplement of sPRR-His, the histidine-tagged sPRR in these models was able to restore circadian variations of BP accompanied with improved rhythms in p-NCC. In vitro data demonstrated that sPRR-His directly reduced abundance of p-NCC but not t-NCC associated with elevated phosphatase activity. Further intriguing in vitro and in vivo evidence suggests that sPRR directly interacted with AT2R to control circadian rhythms of BP and p-NCC. Therefore, we hypothesize that PPARγ-driven adipose-derived sPRR acts via AT2R to dephosphorylate NCC to control circadian rhythm of BP. To test this hypothesis, first, we propose to define adipose tissue as a major source of circulating sPRR during circadian regulation of BP and renal function. Second, we will test whether sPRR signals via AT2R in distal convoluted tubule to activate a specific phosphatase to dephosphorylate NCC. Lastly, we will explore the role of sPRR- His and AT2R agonist C21 as novel chronotherapeutic agents in diet-induced obesity mice. New information resulted from this proposal will help define sPRR-mediated communication between adipose tissue and kidneys in regulation of circadian rhythm of BP.
总结

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 }}

Tianxin Yang其他文献

Tianxin Yang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('Tianxin Yang', 18)}}的其他基金

Adipose-derived sPRR controls circadian rhythm of blood pressure through inhibition of renal NCC activity
脂肪源性 sPRR 通过抑制肾 NCC 活性来控制血压的昼夜节律
  • 批准号:
    10636885
  • 财政年份:
    2022
  • 资助金额:
    $ 63.07万
  • 项目类别:
BLR&D Research Career Scientist Award Application
BLR
  • 批准号:
    10294951
  • 财政年份:
    2020
  • 资助金额:
    $ 63.07万
  • 项目类别:
Defining renal S1P/sPRR/AT1R pathway in salt-sensitive hypertension
盐敏感性高血压肾 S1P/sPRR/AT1R 通路的定义
  • 批准号:
    10293534
  • 财政年份:
    2020
  • 资助金额:
    $ 63.07万
  • 项目类别:
BLR&D Research Career Scientist Award Application
BLR
  • 批准号:
    9995217
  • 财政年份:
    2020
  • 资助金额:
    $ 63.07万
  • 项目类别:
Defining renal S1P/sPRR/AT1R pathway in salt-sensitive hypertension
盐敏感性高血压肾 S1P/sPRR/AT1R 通路的定义
  • 批准号:
    10514577
  • 财政年份:
    2020
  • 资助金额:
    $ 63.07万
  • 项目类别:
BLR&D Research Career Scientist Award Application
BLR
  • 批准号:
    10618276
  • 财政年份:
    2020
  • 资助金额:
    $ 63.07万
  • 项目类别:
BLR&D Research Career Scientist Award Application
BLR
  • 批准号:
    10454237
  • 财政年份:
    2020
  • 资助金额:
    $ 63.07万
  • 项目类别:
Defining renal S1P/sPRR/AT1R pathway in salt-sensitive hypertension
盐敏感性高血压肾 S1P/sPRR/AT1R 通路的定义
  • 批准号:
    9888044
  • 财政年份:
    2020
  • 资助金额:
    $ 63.07万
  • 项目类别:
Role of (pro)renin receptor in aldosterone signaling in the kidney
肾素(原)受体在肾脏醛固酮信号传导中的作用
  • 批准号:
    9921471
  • 财政年份:
    2018
  • 资助金额:
    $ 63.07万
  • 项目类别:
Interaction of (pro)renin receptor and PPARy in regulation of plasma volume
肾素(原)受体和 PPARγ 在血浆容量调节中的相互作用
  • 批准号:
    9729034
  • 财政年份:
    2017
  • 资助金额:
    $ 63.07万
  • 项目类别:

相似国自然基金

Agonist-GPR119-Gs复合物的结构生物学研究
  • 批准号:
    32000851
  • 批准年份:
    2020
  • 资助金额:
    24.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

S1PR1 agonistによる脳血液関門制御を介した脳梗塞の新規治療法開発
S1PR1激动剂调节血脑屏障治疗脑梗塞新方法的开发
  • 批准号:
    24K12256
  • 财政年份:
    2024
  • 资助金额:
    $ 63.07万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
AHR agonistによるSLE皮疹の新たな治療薬の開発
使用 AHR 激动剂开发治疗 SLE 皮疹的新疗法
  • 批准号:
    24K19176
  • 财政年份:
    2024
  • 资助金额:
    $ 63.07万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Evaluation of a specific LXR/PPAR agonist for treatment of Alzheimer's disease
特定 LXR/PPAR 激动剂治疗阿尔茨海默病的评估
  • 批准号:
    10578068
  • 财政年份:
    2023
  • 资助金额:
    $ 63.07万
  • 项目类别:
AUGMENTING THE QUALITY AND DURATION OF THE IMMUNE RESPONSE WITH A NOVEL TLR2 AGONIST-ALUMINUM COMBINATION ADJUVANT
使用新型 TLR2 激动剂-铝组合佐剂增强免疫反应的质量和持续时间
  • 批准号:
    10933287
  • 财政年份:
    2023
  • 资助金额:
    $ 63.07万
  • 项目类别:
Targeting breast cancer microenvironment with small molecule agonist of relaxin receptor
用松弛素受体小分子激动剂靶向乳腺癌微环境
  • 批准号:
    10650593
  • 财政年份:
    2023
  • 资助金额:
    $ 63.07万
  • 项目类别:
AMPKa agonist in attenuating CPT1A inhibition and alcoholic chronic pancreatitis
AMPKa 激动剂减轻 CPT1A 抑制和酒精性慢性胰腺炎
  • 批准号:
    10649275
  • 财政年份:
    2023
  • 资助金额:
    $ 63.07万
  • 项目类别:
Investigating mechanisms underpinning outcomes in people on opioid agonist treatment for OUD: Disentangling sleep and circadian rhythm influences on craving and emotion regulation
研究阿片类激动剂治疗 OUD 患者结果的机制:解开睡眠和昼夜节律对渴望和情绪调节的影响
  • 批准号:
    10784209
  • 财政年份:
    2023
  • 资助金额:
    $ 63.07万
  • 项目类别:
A randomized double-blind placebo controlled Phase 1 SAD study in male and female healthy volunteers to assess safety, pharmacokinetics, and transient biomarker changes by the ABCA1 agonist CS6253
在男性和女性健康志愿者中进行的一项随机双盲安慰剂对照 1 期 SAD 研究,旨在评估 ABCA1 激动剂 CS6253 的安全性、药代动力学和短暂生物标志物变化
  • 批准号:
    10734158
  • 财政年份:
    2023
  • 资助金额:
    $ 63.07万
  • 项目类别:
A novel nanobody-based agonist-redirected checkpoint (ARC) molecule, aPD1-Fc-OX40L, for cancer immunotherapy
一种基于纳米抗体的新型激动剂重定向检查点 (ARC) 分子 aPD1-Fc-OX40L,用于癌症免疫治疗
  • 批准号:
    10580259
  • 财政年份:
    2023
  • 资助金额:
    $ 63.07万
  • 项目类别:
Fentanyl Addiction: Individual Differences, Neural Circuitry, and Treatment with a GLP-1 Receptor Agonist
芬太尼成瘾:个体差异、神经回路和 GLP-1 受体激动剂治疗
  • 批准号:
    10534864
  • 财政年份:
    2023
  • 资助金额:
    $ 63.07万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了