Exfoliative toxin A and desmosomal adhesion in epidermis
Exfoliative toxin A and desmosomal adhesion in epidermis
批准号:
7682888
负责人:
Cory L Simpson
金额:
$5.66万
依托单位国家:
美国
项目类别:
财政年份:
2006
资助国家:
美国
项目状态:
已结题
起止时间:
2006-09-01 至 2010-08-31
关键词:
AdhesionsAdhesivesAntibodiesBindingBiochemicalBiological AssayBiotinBullaCadherinsCanis familiarisCell-Cell AdhesionCellsCleaved cellCo-ImmunoprecipitationsComplexCultured CellsCytoplasmCytoskeletal ModelingDehydrationDesmosomesDiseaseDominant-Negative MutationDoseEpidermisEventExfoliative ToxinsHumanImmunofluorescence MicroscopyImpetigoIn VitroInfectionIntermediate FilamentsLabelLifeLinkMechanicsMediatingMembraneModelingMolecularPathogenesisPlayProtein FamilyProteinsRNA InterferenceResearchResistanceRoleSignal TransductionSkinSolubilityStaphylococcal Scalded Skin SyndromeStaphylococcus aureusStressSyndromeTargeted ToxinsTherapeuticTissuesToxinWorkarmadillo proteinsdesmoglein 1desmoplakinimprovedinhibitor/antagonistkeratinocyteknock-downmonolayermutantnew therapeutic targetpathogenplakoglobinplakophilinsprotein complexprotein transportresearch studyresponsetherapeutic targettrafficking
中文摘要
金黄色葡萄球菌分泌的脱落毒素A(ETA)对人表皮的破坏作用
大疱性脓疱病和葡萄球菌烫伤皮肤综合征(SSSS),使受害者容易患上
危及生命的感染和脱水。桥粒对细胞至关重要:组织中的细胞黏附持久
压力,如表皮。这些蛋白质复合体将中间细丝锚定在细胞连接上,
为皮肤提供必要的机械力量,作为身体的第一道防线
对环境的侮辱。以前的工作表明,ETA裂解桥粒桥粒蛋白1(DSG1)
成分和表层的主要钙粘附素。拟议的研究将确定
DSG1被ETA裂解的特定分子后果导致SSSS。尤其是,
毒素对桥粒成分的运输和相互作用的影响将被调查如下
减少角质形成细胞黏附的机制;以及,诱骗DSG1胞外结构域将被评估为
ETA抑制剂在体外和表皮中的等效物。结果将提供一个更完整的理解
研究SSSS的发病机制,并将确定治疗毒素介导的疾病的新治疗靶点。
英文摘要
Exfoliative toxin A (ETA) secreted by Staphylococcus aureus causes destruction of human epidermis in
bullous impetigo and Staphylcoccal Scalded Skin Syndrome (SSSS), which renders victims vulnerable to
life-threatening infections and dehydration. Desmosomes are crucial for cell:cell adhesion in tissues enduring
stress, such as the epidermis. These protein complexes anchor intermediate filaments to celhcell junctions,
providing the mechanical strength necessary for the skin to serve as the body's first line of defense against
environmental insults. Previous work has shown that ETA cleaves desmoglein 1 (Dsg1), a desmosome
component and the predominant cadherin of the superficial epidermis. The proposed research will determine
the specific molecular consequences of Dsg1 cleavage by ETA that contribute to SSSS. In particular, the
toxin's effects on trafficking of and interactions among desmosomal components will be investigated as
mechanisms reducing adhesion in keratinocytes; as well, a decoy Dsg1 ectodomain will be evaluated as an
ETA inhibitor in vitro and in epidermal equivalents. The results will provide a more complete understanding
of SSSS pathogenesis and will identify novel therapeutic targets for treatment of a toxin-mediated disease.
期刊论文(1)
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会议论文
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依托单位:
海外基金