Mechanisms of Desmosome Regulation and Disassembly in the Skin Disease Pemphigus
皮肤病天疱疮中桥粒调节和分解的机制
基本信息
- 批准号:8117123
- 负责人:
- 金额:$ 32.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-08-01 至 2013-07-31
- 项目状态:已结题
- 来源:
- 关键词:AdhesionsAdhesivesAmino AcidsAntibodiesAutoantibodiesAutoimmune DiseasesBiologyBullaCadherinsCell Adhesion MoleculesCell Culture TechniquesCell surfaceCell-Cell AdhesionCellsCharacteristicsCouplesCytokeratin filamentsCytoplasmic TailCytoskeletal ModelingDesmosomesDiseaseEndocytosisExposure toFunctional disorderFundingGoalsImmunoglobulin GIn VitroInborn Genetic DiseasesIndividualIntercellular JunctionsIntermediate FilamentsKeratinLaboratoriesLeadLifeMediatingMembrane Protein TrafficMicroscopyModelingMolecularMucous MembraneMusPathogenicityPathway interactionsPatientsPemphigusPemphigus VulgarisPhasePlayProcessProteinsReagentRegulationResearch DesignRoleSeriesSignal PathwaySkinStructureTailTestingTherapeuticWorkarmadillo proteinsbasedesmoglein IIIdesmoplakinhuman monoclonal antibodiesinsightkeratinocytemembernew therapeutic targetnovel therapeutic interventionplakophilinspreventprotein complexresponseskin disorder
项目摘要
DESCRIPTION (provided by applicant): Pemphigus is a class of devastating epidermal blistering diseases in which autoantibodies are generated against cell-cell adhesion molecules present in the skin and mucous membranes. Pemphigus IgG target desmosomes, a structure that couples the keratin intermediate filament network to regions of strong cell-cell adhesion. In pemphigus vulgaris (PV), the primary target of the autoantibodies is desmoglein-3 (Dsg3), a member of the desmosomal cadherin subfamily of adhesion molecules. The work outlined in this application investigates the mechanisms by which IgG from pemphigus vulgaris patients disrupts cell-cell adhesion. It is hypothesized that PV IgG disrupt desmosomes by causing Dsg3 internalization from the cell surface, leading to desmosome destabilization and loss of keratinocyte adhesion. This hypothesis will be tested using a series of in vitro cell culture models that employ cellular and molecular approaches to define the mechanisms by which PV IgG cause Dsg3 internalization and desmosome disassembly. These studies will reveal the cellular machinery and pathways that mediate Dsg3 endocytosis, and how cytoplasmic components of the desmosome regulate Dsg3 internalization. Furthermore, a panel of antibody reagents will be employed, including PV patient IgG, human monoclonal antibodies cloned from patients, and mouse monoclonal Dsg3 antibodies with varying degrees of pathogenic activity. These reagents will be used to reveal relationships between desmosome disassembly pathways and antibody pathogenicity profiles to determine how pemphigus IgG causes disease at the cellular level. RELEVANCE: These studies are designed to generate new insights into the basic cellular mechanisms that regulate cell-cell adhesion, and to expose new therapeutic targets for the treatment of pemphigus and other skin diseases characterized by epidermal fragility.
描述(申请人提供):天疱疮是一种破坏性的表皮起泡性疾病,在这种疾病中,针对存在于皮肤和粘膜中的细胞-细胞黏附分子产生自身抗体。天疱疮免疫球蛋白以桥粒为靶标,桥粒是一种将角蛋白中间细丝网络连接到细胞间粘附性强的区域的结构。在寻常型天疱疮(PV)中,自身抗体的主要靶点是桥粒钙粘附素亚家族成员桥粒钙粘附素-3(Dsg3)。本申请概述的工作是研究寻常型天疱疮患者的免疫球蛋白破坏细胞间黏附的机制。推测PV-Ig G通过引起Dsg3从细胞表面内化而破坏桥粒,导致桥粒失稳和角质形成细胞黏附丧失。这一假设将通过一系列体外细胞培养模型进行验证,这些模型使用细胞和分子方法来确定PV IgG导致Dsg3内化和桥粒拆解的机制。这些研究将揭示介导Dsg3内吞作用的细胞机制和途径,以及桥粒的细胞质成分如何调节Dsg3内化。此外,还将使用一组抗体试剂,包括PV患者的IgG、从患者克隆的人源单抗和具有不同致病活性的鼠单抗Dsg3。这些试剂将用于揭示桥粒分解途径和抗体致病性之间的关系,以确定天疱疮免疫球蛋白是如何在细胞水平上导致疾病的。相关性:这些研究旨在对调节细胞间黏附的基本细胞机制产生新的见解,并揭示天疱疮和其他以表皮脆性为特征的皮肤病的治疗新靶点。
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 }}
ANDREW P. KOWALCZYK其他文献
ANDREW P. KOWALCZYK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('ANDREW P. KOWALCZYK', 18)}}的其他基金
Keratinocyte adhesion and signaling in the skin blistering disease pemphigus vulgaris
皮肤起疱病寻常型天疱疮中的角质形成细胞粘附和信号传导
- 批准号:
10732360 - 财政年份:2023
- 资助金额:
$ 32.41万 - 项目类别:
Cadherin regulation in dermal endothelial cells
真皮内皮细胞中钙粘蛋白的调节
- 批准号:
8526381 - 财政年份:2004
- 资助金额:
$ 32.41万 - 项目类别:
Cadherin Regulation in Dermal Endothelial Cells
真皮内皮细胞中钙粘蛋白的调节
- 批准号:
9381479 - 财政年份:2004
- 资助金额:
$ 32.41万 - 项目类别:
Cadherin Regulation in Dermal Endothelial Cells
真皮内皮细胞中钙粘蛋白的调节
- 批准号:
7227094 - 财政年份:2004
- 资助金额:
$ 32.41万 - 项目类别:
Cadherin Regulation in Dermal Endothelial Cells
真皮内皮细胞中钙粘蛋白的调节
- 批准号:
6929228 - 财政年份:2004
- 资助金额:
$ 32.41万 - 项目类别:
Cadherin Regulation in Dermal Endothelial Cells
真皮内皮细胞中钙粘蛋白的调节
- 批准号:
6820500 - 财政年份:2004
- 资助金额:
$ 32.41万 - 项目类别:
Cadherin Regulation in Dermal Endothelial Cells
真皮内皮细胞中钙粘蛋白的调节
- 批准号:
9982790 - 财政年份:2004
- 资助金额:
$ 32.41万 - 项目类别:
Cadherin Regulation in Dermal Endothelial Cells
真皮内皮细胞中钙粘蛋白的调节
- 批准号:
9752474 - 财政年份:2004
- 资助金额:
$ 32.41万 - 项目类别:
Cadherin regulation in dermal endothelial cells
真皮内皮细胞中钙粘蛋白的调节
- 批准号:
7727763 - 财政年份:2004
- 资助金额:
$ 32.41万 - 项目类别:
Cadherin regulation in dermal endothelial cells
真皮内皮细胞中钙粘蛋白的调节
- 批准号:
8185601 - 财政年份:2004
- 资助金额:
$ 32.41万 - 项目类别:
相似海外基金
I-Corps: Translation Potential of Peptidic Ensembles as Novel Bio-adhesives
I-Corps:肽整体作为新型生物粘合剂的转化潜力
- 批准号:
2409620 - 财政年份:2024
- 资助金额:
$ 32.41万 - 项目类别:
Standard Grant
Architectural design of active adhesives
活性粘合剂的结构设计
- 批准号:
2403716 - 财政年份:2024
- 资助金额:
$ 32.41万 - 项目类别:
Standard Grant
Design of non-swellable adhesives for brain surgery using cyclodextrin inclusion polymer
使用环糊精包合物聚合物脑外科不可溶胀粘合剂的设计
- 批准号:
23H01718 - 财政年份:2023
- 资助金额:
$ 32.41万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Meta-material adhesives for improved performance and functionalisation of bondlines
超材料粘合剂可提高粘合层的性能和功能化
- 批准号:
EP/W019450/1 - 财政年份:2023
- 资助金额:
$ 32.41万 - 项目类别:
Fellowship
Light-propelled dental adhesives with enhanced bonding capability
具有增强粘合能力的光驱动牙科粘合剂
- 批准号:
10741660 - 财政年份:2023
- 资助金额:
$ 32.41万 - 项目类别:
DMREF: Accelerating the Design of Adhesives with Nanoscale Control of Thermomechanical Properties
DMREF:通过热机械性能的纳米级控制加速粘合剂的设计
- 批准号:
2323317 - 财政年份:2023
- 资助金额:
$ 32.41万 - 项目类别:
Continuing Grant
Mag-Cure: A novel method for magnetically induced bonding and de-bonding of thermoset adhesives in the Automotive Industry
Mag-Cure:汽车行业中热固性粘合剂磁感应粘合和脱粘的新方法
- 批准号:
10062336 - 财政年份:2023
- 资助金额:
$ 32.41万 - 项目类别:
Collaborative R&D
Biodegradable, Biocompatible Pressure Sensitive Adhesives
可生物降解、生物相容性压敏粘合剂
- 批准号:
10677869 - 财政年份:2022
- 资助金额:
$ 32.41万 - 项目类别:
Poly(glycerol carbonate) pressure sensitive adhesives for the in vivo closure of alveolar pleural fistulae
用于体内闭合肺泡胸膜瘘的聚(甘油碳酸酯)压敏粘合剂
- 批准号:
10746743 - 财政年份:2022
- 资助金额:
$ 32.41万 - 项目类别:
Enhanced bio-production of difficult to make peptide ingredients for specialty adhesives and personal care
增强用于特种粘合剂和个人护理品的难以制造的肽成分的生物生产
- 批准号:
10021363 - 财政年份:2022
- 资助金额:
$ 32.41万 - 项目类别:
Investment Accelerator