Role of Cilia in Renal Fibrosis
纤毛在肾纤维化中的作用
基本信息
- 批准号:10153778
- 负责人:
- 金额:$ 37.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-15 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AffectBackCell surfaceCellsCiliaCommunicationComplexCystCystic kidneyDefectDiseaseDisease ProgressionDistalEpithelialEpithelial CellsErinaceidaeFeedsFibroblastsFibrosisGenesKidneyKnockout MiceLeadLigandsMental RetardationModelingMonomeric GTP-Binding ProteinsMusMutant Strains MiceMyofibroblastNephronophthisisNephronsObesityOrganellesPathway interactionsPatternPhenotypePolycystic Kidney DiseasesRetinal DegenerationRoleSignal PathwaySignal TransductionSmooth Muscle Actin Staining MethodTestingTissuesbasecell typeciliopathycilium biogenesishuman diseaseinsightinterstitialinterstitial cellkidney fibrosismutantparacrinerenal epitheliumresponsesmoothened signaling pathway
项目摘要
Summary
The cilium is a widely distributed cell surface organelle that functions as a signaling hub for the vertebrate cell.
Ciliary defects leads to a wide range of human diseases collectively referred to as ciliopathies. Multiple
ciliopathies, including nephronophthisis, show renal fibrosis. However, the role of cilia in renal fibrosis has not
been studied extensively. In this project, we use Arl13b, a gene essential for cilia biogenesis, as an entry point
to dissect the role of cilia in renal fibrosis. We generated conditional Arl13b knockout mice. Our results show
that deletion of Arl13b in renal epithelial cells leads to renal fibrosis and cysts. Moreover, multiple signaling
pathways, including the Wnt, HH and Hippo pathway, are mis-regulated in the mutant kidney. This project
focuses on dissecting tissue specific functions of cilia and communications between different cell types in renal
fibrosis through both candidate and unbiased approaches. Aim 1 is focused on signaling in renal epithelial cells
regulated by ciliary defects and the relationship between different pathways. Aim 2 studies targets in interstitial
cells that are affected by ciliary defects and the functional significance of interstitial cilia. Through this study, we
will elucidate how ciliary defects in epithelial cells triggers a signaling cascade that eventually lead to renal
fibrosis and whether and how cilia in interstitial cells modify this response. These results not only will provide
insight to the mechanism of renal fibrosis in ciliopathies, but will also be informative to fibrosis in general.
摘要
纤毛是一种广泛分布的细胞表面细胞器,是脊椎动物细胞的信号中枢。
纤毛缺陷会导致一系列人类疾病,统称为纤毛疾病。多重
纤毛病变,包括肾小球肾炎,表现为肾纤维化。然而,纤毛在肾纤维化中的作用并不是
得到了广泛的研究。在这个项目中,我们使用了纤毛生物发生所必需的基因Arl13b作为切入点
目的:探讨纤毛在肾纤维化中的作用。我们产生了条件性Arl13b基因敲除小鼠。我们的结果显示
肾上皮细胞Arl13b缺失会导致肾纤维化和肾囊肿。此外,多路信令
在突变的肾脏中,包括Wnt、HH和Hippo途径在内的途径被错误地调节。这个项目
重点解剖肾脏纤毛的组织特定功能和不同细胞类型之间的通讯
通过候选和不偏不倚的方法进行纤维化。AIM 1主要研究肾上皮细胞中的信号转导
受睫状体缺陷和不同通路之间的关系的调节。目的2研究间质中的靶点
受纤毛缺陷影响的细胞和间质纤毛的功能意义。通过这项研究,我们
将阐明上皮细胞中的纤毛缺陷如何触发信号级联,最终导致肾脏
纤维化和间质细胞中的纤毛是否以及如何改变这种反应。这些结果不仅将提供
深入了解纤毛病变中肾纤维化的机制,但也将有助于了解纤维化的一般情况。
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)
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ZHAOXIA SUN其他文献
ZHAOXIA SUN的其他文献
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{{ truncateString('ZHAOXIA SUN', 18)}}的其他基金
Mechanism and Regulation of Axonemal Dynein Arm Assembly in Motile Ciliated Epithelial Cells
运动纤毛上皮细胞轴丝动力蛋白臂组装的机制和调控
- 批准号:
10930194 - 财政年份:2023
- 资助金额:
$ 37.69万 - 项目类别:
Genetic Analysis of Organ Patterning Defects in Ciliopathies
纤毛病器官模式缺陷的遗传分析
- 批准号:
10251032 - 财政年份:2018
- 资助金额:
$ 37.69万 - 项目类别:
Genetic Analysis of Organ Patterning Defects in Ciliopathies
纤毛病器官模式缺陷的遗传分析
- 批准号:
10011885 - 财政年份:2018
- 资助金额:
$ 37.69万 - 项目类别:
Genetic Analysis of Organ Patterning Defects in Ciliopathies
纤毛病器官模式缺陷的遗传分析
- 批准号:
10477030 - 财政年份:2018
- 资助金额:
$ 37.69万 - 项目类别:
NPHP2 in ciliary function, renal fibrosis and cyst formation
NPHP2 在纤毛功能、肾纤维化和囊肿形成中的作用
- 批准号:
10736919 - 财政年份:2017
- 资助金额:
$ 37.69万 - 项目类别:
Investigate kidney cyst formation and a cilia-mediated signaling network
研究肾囊肿的形成和纤毛介导的信号网络
- 批准号:
8685254 - 财政年份:2012
- 资助金额:
$ 37.69万 - 项目类别:
Investigate kidney cyst formation and a cilia-mediated signaling network
研究肾囊肿的形成和纤毛介导的信号网络
- 批准号:
8297035 - 财政年份:2012
- 资助金额:
$ 37.69万 - 项目类别:
Investigate kidney cyst formation and a cilia-mediated signaling network
研究肾囊肿的形成和纤毛介导的信号网络
- 批准号:
8472493 - 财政年份:2012
- 资助金额:
$ 37.69万 - 项目类别:
Sco, A Zebrafish Model Links Cilia and Kidney Cysts
Sco,斑马鱼模型将纤毛和肾囊肿联系起来
- 批准号:
7069661 - 财政年份:2005
- 资助金额:
$ 37.69万 - 项目类别:
Sco, A Zebrafish Model Links Cilia and Kidney Cysts
Sco,斑马鱼模型将纤毛和肾囊肿联系起来
- 批准号:
7617568 - 财政年份:2005
- 资助金额:
$ 37.69万 - 项目类别:
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