Wound healing mechanisms modulated by novel antimicrobial Peptides
Wound healing mechanisms modulated by novel antimicrobial Peptides
批准号:
9182311
负责人:
Anne Kasus-Jacobi
金额:
$18.5万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-30 至 2018-08-31
关键词:
AdhesionsAntibiotic ResistanceAntibioticsAntimicrobial EffectBacteriaBacterial InfectionsBindingBiological ProcessBlindnessCellsClinicClinicalCo-ImmunoprecipitationsComplexCorneaCorneal AbrasionCorneal InjuryDermalDevelopmentDiseaseEnsureEpithelial CellsEventEye InjuriesG-Protein-Coupled ReceptorsGoalsHealedHealthHumanImmune systemInfectionInflammationIntracellular MembranesIntracellular Signaling ProteinsInvadedInvestigationKeratitisKnowledgeLeadLengthLigand BindingLigandsMediatingMediator of activation proteinMembraneMethodsMolecularMusNational Eye InstituteOne-Step dentin bonding systemPeptidesPreventionProcessProtein AnalysisProtein IsoformsProteinsRNA analysisReportingResearchResistanceRisk FactorsRoleSignal PathwaySignal TransductionStructureTertiary Protein StructureTestingTherapeuticTimeTranslatingUnited StatesVisionWorkWound Healinganalogantimicrobialantimicrobial peptidebasecell motilityclinical applicationcorneal epitheliumextracellularhealinghuman migrationimproved outcomein vivoinhibitor/antagonistinnovationkillingsknock-downmigrationnovelnovel therapeuticsopen woundpathogenpeptide analogpeptide drugpreventreceptorreceptor bindingresearch studyresponsewound
中文摘要
描述:伤口愈合是一个复杂的过程,遵循一系列确定的事件,包括
英文摘要
DESCRIPTION: Wound healing is a complex process that follows a defined sequence of events consisting of
inflammation, proliferation and migration of epithelial cells to re-epithelialize the wound, and
remodeling/differentiation. The cationic antimicrobial protein of 37 kDa (CAP37) belongs to the innate immune
system and was originally identified based on its powerful antimicrobial effect. It was later found to induce
migration, adhesion and proliferation of cultured corneal epithelial cells, which translated into faster corneal re-
epithelialization in vivo. Structure-function studies of CAP37 were initiated with the long-term goal to identify
the antimicrobial and the wound healing domains of the protein to generate therapeutic peptides for clinical
use. Our lab recently identified two CAP37-derived peptide analogs that carry a strong antimicrobial activity,
even on antibiotic resistant or multiresistant strains, and a wound healing activity. These analogs have strong
potential to be used as innovative ocular treatments with the dual effects of promoting corneal re-
epithelialization and preventing or clearing bacterial infections.
The molecular mechanisms mediating the wound healing effects of the full length CAP37 and the two derived
analogs are unknown. The objective of this proposal is to identify the membrane and intracellular mediators
activated by these extracellular ligands to induce migration of immortalized corneal epithelial cells and corneal
re-epithelialization in mouse. Based on previous studies in our lab, we hypothesize that CAP37 and derived
analogs act as extracellular ligands, binding a G protein-coupled receptor (GPCR) on corneal epithelial cells to
activate intracellular signaling pathways, including the signal transduction proteins PKCδ and PKCθ, thus
promoting wound healing effects. Two specific aims are proposed. (1) To identify the receptor(s) mediating the
migration of human corneal epithelial cells and corneal wound healing in response to CAP37 ligands. (2) To
identify the downstream signaling pathway(s) mediating corneal epithelial cell migration and corneal wound
healing in response to CAP37 ligands. This new knowledge will break new grounds in this field of research
because a receptor for CAP37 will be identified for the first time since its discovery 30 years ago. This new
knowledge will also be key to developing and optimizing CAP37-derived peptide analogs into innovative
therapeutics with the dual effects of killing resistant pathogens and promoting wound healing.
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PHOTORECEPTOR RETINOL DEHYDROGENASES AND VISION
-
批准号:8168350
-
项目类别:
-
资助金额:$10.95万
-
财政年份:2010
-
负责人:Anne Kasus-Jacobi
-
依托单位:
PHOTORECEPTOR RETINOL DEHYDROGENASES AND VISION
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批准号:7959977
-
项目类别:
-
资助金额:$21.91万
-
财政年份:2009
-
负责人:Anne Kasus-Jacobi
-
依托单位:
UNDERSTANDING THE ROLE OF RETINOL DEHYDROGENASES RDH11 AND RDH12 IN VISION
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批准号:7720540
-
项目类别:
-
资助金额:$21.5万
-
财政年份:2008
-
负责人:Anne Kasus-Jacobi
-
依托单位:
Detoxification Role of Retinol Dehydrogenases RDH11 and RDH12
-
批准号:7530623
-
项目类别:
-
资助金额:$21.98万
-
财政年份:2008
-
负责人:Anne Kasus-Jacobi
-
依托单位:
Detoxification Role of Retinol Dehydrogenases RDH11 and RDH12
-
批准号:7689187
-
项目类别:
-
资助金额:$18.31万
-
财政年份:2008
-
负责人:Anne Kasus-Jacobi
-
依托单位:
Structural Approach to Define New Functional Activities of Neutrophil Protein CAP37 in Neurodegenerative Diseases(Kasus-Jacobi)
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批准号:9360241
-
项目类别:
-
资助金额:$20.66万
-
财政年份:--
-
负责人:Anne Kasus-Jacobi
-
依托单位:
海外基金