Regulation of Lymphatic Endothelial Cell Junction and Drainage
淋巴内皮细胞连接和引流的调节
基本信息
- 批准号:10642883
- 负责人:
- 金额:$ 47.54万
- 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 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAlzheimer&aposs DiseaseAnimal ModelArchitectureArthritisBindingBiologicalBiologyBiomedical EngineeringBiophysicsBlood VesselsBostonBrainCell Culture TechniquesCellsClinical ResearchCollaborationsComplexDevelopmentDietary FatsDiseaseDrainage procedureExhibitsExperimental ModelsFibronectinsFibrosisFluid BalanceGlaucomaGoalsHomeostasisHumanITGA5 geneImmune System DiseasesImmunityImmunologistIn VitroInflammationInflammatoryInflammatory ResponseIntercellular FluidIntercellular JunctionsLigandsLiquid substanceLymphLymphaticLymphatic DiseasesLymphatic Endothelial CellsLymphatic EndotheliumLymphatic SystemLymphatic functionLymphedemaMalignant NeoplasmsMediatingMeningeal lymphatic systemMetabolic DiseasesModelingMorphogenesisMorphologyMusNeurodegenerative DisordersNeuronsObesityOrganOutcomePediatric HospitalsPericytesPermeabilityPhysiologicalProtein KinaseROCK1 geneRegulationResearch PersonnelRoleSignal TransductionSmall IntestinesStructureTissuesTreatment EfficacyUniversitiesVascular Systemdrug candidatehuman diseasein vitro Modelin vivoin vivo Modelinhibitorlacteallymph nodeslymphatic drainagelymphatic dysfunctionlymphatic vesselrhoscreeningtherapeutic evaluationthree-dimensional modelingtooltwo-dimensionaluptakewasting
项目摘要
PROJECT SUMMARY
Lymphatic vessel (LV) differentiation, development, and morphogenesis are central in maintaining fluid
homeostasis, regulating host immunity, and transporting dietary fat and neuronal waste. All these functions
are governed by lymphatic drainage, a transport of interstitial fluid into the lymphatic system through the initial
LVs and collecting LVs. The initial LVs show permeable button-like junction morphology and are ready to
uptake interstitial fluid; by contrast, the collecting LVs are less permeable with zipper-like junction structure,
so that the collecting LVs transport ‘lymph’ to lymph nodes without leaking. Impaired lymphatic drainage
contributes to many human diseases, such as lymphedema, immune dysfunction, fibrosis, obesity, cancer,
and Alzheimer’s disease. While little is known about why LVs become dysfunctional, clinical studies reveal
that inflammation is one of the leading contributors to the lymphatic dysfunction. Although dysfunctional
collecting LVs has been extensively studied, how inflammation impacts initial LV development and
morphogenesis is unclear, because in our current experimental models, including animal models, we often
cannot decouple multifactorial inflammatory factors in the lymphatic endothelium. Since two-dimensional cell
culture has failed to recapitulate three-dimensional (3D) tissue architecture of lymphatics, researchers have
developed 3D in vitro models of LVs, demonstrating lymphatic sprouting, lymphatic network formation, and
LV interactions with other cells. However, these previous models have not created 3D lymphatic structure
with specialized LEC junction development enabling controlled fluid drainage through the button-like
junctions and physiological inflammatory response. In this proposal, we will use a bioengineered in vitro 3D
lymphatic vascular system, exhibiting button-like junction morphogenesis of the LVs and fluid drainage to
understand the regulation of LEC junction and drainage by focusing on ROCK1/2 and integrin α5 signaling.
In Aim 1, we will examine the roles of ROCKs in LEC junction and drainage. Next, we will scrutinize the
mechanisms of ROCKs-mediated junction zippering in LECs. In Aim 2, we will study integrin α5 mediated
regulation of LEC junction and lymphatic drainage. We will then determine signal transduction through
ROCKs and integrin α5 and evaluate therapeutic efficacy of targeting ROCKs and integrin α5 in lymphatic
dysfunction and inflammation models in vivo. In summary, we will use a bioengineered model of 3D lymphatic
vessels and fluid transport to provide an understanding of lymphatic drainage in normal and inflammatory
conditions.
项目总结
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)
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Esak Lee其他文献
Esak Lee的其他文献
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{{ truncateString('Esak Lee', 18)}}的其他基金
Tissue-Engineered Models of Lymphatic Drainage in Breast Cancer
乳腺癌淋巴引流的组织工程模型
- 批准号:
10637169 - 财政年份:2023
- 资助金额:
$ 47.54万 - 项目类别:
A Bioengineered Model of Tumor Vessel Interactions in Pancreatic Cancer
胰腺癌肿瘤血管相互作用的生物工程模型
- 批准号:
10373531 - 财政年份:2022
- 资助金额:
$ 47.54万 - 项目类别:
Regulation of Lymphatic Endothelial Cell Junction and Drainage
淋巴内皮细胞连接和引流的调节
- 批准号:
10502991 - 财政年份:2022
- 资助金额:
$ 47.54万 - 项目类别:
A Bioengineered Model of Tumor Vessel Interactions in Pancreatic Cancer
胰腺癌肿瘤血管相互作用的生物工程模型
- 批准号:
10557226 - 财政年份:2022
- 资助金额:
$ 47.54万 - 项目类别:
A Bioengineered Model for Deciphering Lymphatic Dysfunction in Inflammation
破译炎症中淋巴功能障碍的生物工程模型
- 批准号:
10493273 - 财政年份:2021
- 资助金额:
$ 47.54万 - 项目类别:
A Bioengineered Model for Deciphering Lymphatic Dysfunction in Inflammation
破译炎症中淋巴功能障碍的生物工程模型
- 批准号:
10354568 - 财政年份:2021
- 资助金额:
$ 47.54万 - 项目类别:














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