The ILK/PINCH/Parvin complex in renal tubulogenesis

ILK/PINCH/Parvin 复合物在肾小管发生中的作用

基本信息

  • 批准号:
    8687966
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-04-01 至 2017-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Our overall goal is to define the molecular mechanisms whereby cell-extracellular matrix (ECM) interactions regulate renal tubulogenesis. Renal tubules are highly ordered terminally differentiated structures consisting of polarized epithelial cells derived from either the ureteric bud (UB) or the metanephric mesenchyme (MM). Because biological changes occurring during renal tubulogenesis are best characterized in the context of renal development, we use the UB as a model to study basic mechanisms of tubule formation. However these processes are also critically important in understanding the pathophysiology of congenital renal diseases such as polycystic kidney disease and renal dysplasia which affect the adult Veteran population. Furthermore, many features of renal tubule development are recapitulated in renal recovery following acute kidney tubule injury, which is a major cause of morbidity and mortality in Veterans. The UB originates from the Wolffian duct and gives rise to the collecting system of the mature kidney from the collecting ducts (CD) to the trigone of the bladder. The renal papilla and CDs develop by undergoing iterative branching morphogenesis, a complex process that is, at least in part, dependent on cell-ECM interactions. We previously demonstrated that integrins are critical for tubulogenesis. Integrins are transmembrane receptors for ECM composed of non-covalently bound and subunits. 1 is the most abundantly expressed integrin subunit in the kidney and can bind 12 different a subunits. The 1 cytoplasmic tail plays a critical role in integrn function by binding multiple cytoplasmic proteins which regulate integrin- mediated signaling and cytoskeleton modulation. The integrin linked kinase (ILK)/Pinch/Parvin (IPP) complex is one of the key scaffolding hubs that bind the integrin 1 cytoplasmic tail. We previously showed that ILK and Pinch are critical for tubule formation; however, the role of Parvin is still unknown. In this Merit renewal we will define how the IPP complex interacts with the 1 integrin tail and how specific interactions among the various IPP components regulate renal tubulogenesis by testing the hypotheses that a) distinct IPP components have specific roles in mediating renal tubulogenesis and b) IPP/1 integrin interactions are dynamically regulated by certain 1 tail residues. To test these hypotheses we will perform the following 3 aims. 1) Determine the mechanisms whereby ILK regulates development and maintenance of the kidney collecting system. 2) Determine the role of Parvin in the development and maintenance of the kidney collecting system. 3) Determine the mechanism whereby the 1 integrin cytoplasmic tail recruits the IPP complex. This study will generate novel insights into the molecular basis whereby 1 integrins and the ILK/Pinch/Parvin complex regulate renal tubulogenesis. Understanding this basic cell biological process will help with our comprehension of the pathophysiology of congenital renal diseases resulting in abnormal tubule formation as well as how tubules recover from acute injury. Ultimately a better understanding of these processes might lead to novel therapeutics for the treatment of renal disease caused by dysregulated tubule formation.
描述(由申请人提供): 我们的总体目标是确定细胞-细胞外基质(ECM)相互作用调节肾小管形成的分子机制。肾小管是高度有序的终末分化结构,由来自输尿管上皮细胞和肾小管上皮细胞的极化上皮细胞组成。 芽(UB)或后肾间充质(MM)。由于肾小管形成过程中发生的生物学变化在肾脏发育的背景下得到最好的表征,我们使用UB作为模型来研究肾小管形成的基本机制。然而,这些过程对于理解影响成年退伍军人群体的先天性肾脏疾病(如多囊肾病和肾发育不良)的病理生理学也至关重要。此外,肾小管发育的许多特征在急性肾小管损伤后的肾恢复中重现,这是退伍军人发病率和死亡率的主要原因。 UB起源于Wolffian管,并从集合管(CD)到膀胱三角区形成成熟肾脏的集合系统。肾乳头和CD通过经历反复的分支形态发生而发展,这是一个复杂的过程,至少部分依赖于细胞-ECM相互作用。我们以前证明,整合素是至关重要的小管。整合素是ECM的跨膜受体,由非共价结合的和亚基组成。1是肾脏中表达最丰富的整联蛋白亚基,可以结合12种不同的α亚基。1胞质尾区通过结合多种胞质蛋白调节整合素介导的信号传导和细胞骨架调节在整合素功能中起关键作用。整合素连接激酶(ILK)/Pinch/Parvin(IPP)复合物是结合整合素1胞质尾区的关键支架枢纽之一。我们先前表明ILK和Pinch对小管形成至关重要;然而,Parvin的作用仍然未知。在本次Merit更新中,我们将通过检验以下假设来定义IPP复合物如何与1整联蛋白尾部相互作用以及各种IPP组分之间的特异性相互作用如何调节肾小管形成:a)不同的IPP组分在介导肾小管形成中具有特定作用,以及B)IPP/1整联蛋白相互作用受某些1尾部残基的动态调节。为了验证这些假设,我们将执行以下3个目标。1)确定ILK调节肾脏收集系统发育和维持的机制。2)确定Parvin在肾脏收集系统的发育和维持中的作用。3)确定1整合素胞质尾区募集IPP复合物的机制。 这项研究将产生新的见解的分子基础,其中1整合素和ILK/捏/Parvin复合物调节肾小管。了解这一基本的细胞生物学过程将有助于我们理解导致异常肾小管形成的先天性肾脏疾病的病理生理学以及肾小管如何从急性损伤中恢复。最终,更好地了解这些过程可能会导致新的治疗方法,用于治疗由肾小管形成失调引起的肾脏疾病。

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 }}

ROY ZENT其他文献

ROY ZENT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('ROY ZENT', 18)}}的其他基金

The Laminin Receptors in Kidney Fibrosis
肾纤维化中的层粘连蛋白受体
  • 批准号:
    9914510
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
The Laminin Receptors in Kidney Fibrosis
肾纤维化中的层粘连蛋白受体
  • 批准号:
    10186731
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
The Laminin Receptors in Kidney Fibrosis
肾纤维化中的层粘连蛋白受体
  • 批准号:
    10368972
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
ORD Shared Equipment Evaluation Program (ShEEP) (IS1) - Zeiss LSM980 Airyscan Confocal Microscope
ORD 共享设备评估计划 (ShEEP) (IS1) - Zeiss LSM980 Airyscan 共焦显微镜
  • 批准号:
    10180502
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
2019 Fibronectin, Integrins and Related Molecules GRC/GRS
2019 纤连蛋白、整合素及相关分子 GRC/GRS
  • 批准号:
    9751563
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
Vanderbilt O'Brien Kidney Center - Core C Cell and Genome Engineering
范德比尔特奥布莱恩肾脏中心 - 核心 C 细胞和基因组工程
  • 批准号:
    10163168
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
The ILK/PINCH/Parvin complex in renal tubulogenesis
ILK/PINCH/Parvin 复合物在肾小管发生中的作用
  • 批准号:
    8543139
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
lntegrin binding proteins and the kidney
整合素结合蛋白和肾脏
  • 批准号:
    10587019
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
The ILK/PINCH/Parvin complex in renal tubulogenesis
ILK/PINCH/Parvin 复合物在肾小管发生中的作用
  • 批准号:
    8803371
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Betal Integrin and Renal Tubulogenesis
β整合素和肾小管发生
  • 批准号:
    8668041
  • 财政年份:
    2008
  • 资助金额:
    --
  • 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:
    --
  • 项目类别:
    Research 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:
    --
  • 项目类别:
    Standard 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了