MFAP5 and Skin Scar Formation
MFAP5 和皮肤疤痕形成
基本信息
- 批准号:10605379
- 负责人:
- 金额:$ 5.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-02 至 2027-05-01
- 项目状态:未结题
- 来源:
- 关键词:AdultAffectApoptoticArchitectureAreaBioinformaticsBiological AssayCellsChemoresistanceCicatrixCollagenComplexContractureDataDevelopmentDiseaseEstheticsExtracellular MatrixFibroblastsFibrosisGene ExpressionGenesGenomicsGoalsHemostatic functionHumanHypertrophic CicatrixImpairmentIn VitroInflammationInflammatoryIngestionInstitutionKeloidKnockout MiceLeadLinkLiver CirrhosisMFAP1 geneMalignant NeoplasmsMediatorMicrofibrilsMusMyocardial InfarctionMyofibroblastOntologyOrganOutcomePainPathogenesisPathologicPathway AnalysisPathway interactionsPatientsPhagocytesPhasePhenotypeProcessProductionPrognostic MarkerProliferatingProteinsPulmonary FibrosisRNARegulationResearchResearch PersonnelResearch TrainingResourcesRoleSignal PathwaySignal TransductionSkinSkin wound healingSourceSurfaceSystemic SclerodermaTechniquesTissuesTrainingTransfectionUp-RegulationWidthWorkangiogenesisbody systemcareer developmentcell motilitycomparison controldesigndifferential expressionexperimental studyextracellularfibrillinhealinghuman diseaseidiopathic pulmonary fibrosisin vivolaboratory experimentmigrationnovelnovel therapeuticsoverexpressionrecruitrepair functionresponsesingle-cell RNA sequencingskin fibrosisskin regenerationtargeted biomarkertherapeutic biomarkertissue injurytissue repairtranscriptometranscriptome sequencingvectorwoundwound closurewound healing
项目摘要
PROJECT SUMMARY
This application proposes a customized research training plan designed to promote the development of the
applicant into an independent investigator. The plan includes advanced training in both bioinformatics and
laboratory experimentation, along with tailored professional and career development opportunities. The training
plan is supported by the outstanding availability of local and institutional resources at UIC. The proposed
research will examine the mechanisms that control scar formation, a common result of the healing response. In
adults, the outcome of wound repair is almost always a fibrous scar composed of disorganized extracellular
matrix (ECM). Although regulation of scar formation is complex, a key feature is fibroblast (FB) activation,
which generates ECM and contractile forces. Scarring and fibrosis occurs in many tissues and can cause
significant impairments of the organ system affected. Recent studies in our lab have identified a novel FB
function in wounds that may be linked to scar formation. These studies show that wound FBs can act as non-
professional phagocytes and ingest apoptotic cells. Following apoptotic cell engulfment, FBs develop a fibrotic
phenotype with enhanced migration, increased contractility (α-SMA expression), and increased collagen
synthesis. One factor found to be significantly upregulated in fibrotic phagocytic FBs is microfibril-associated
protein 5 (MFAP5 or microfibril-associated glycoprotein 2/MAGP2). MFAP5 influences microfibril function and
can regulate cell signaling pathways. Interestingly, MFAP5 has been linked to fibrosis in several human
diseases, including some cancers and fibrotic diseases. Still, little is known regarding its role in wound healing
and scar formation. Therefore, the goal of this study is to gain a better understanding of the function of MFAP5
in skin healing and scar formation. We hypothesize that upregulation of MFAP5 in the healing skin wound
modifies the FB response and promotes scar formation. In this study, the role of MFAP5 in wound healing
will be investigated in Mfap5-/- mice, a well-established Mfap5 knock out mouse line. The effect of MFAP5 on
FB phenotype will be further investigated in vitro. This proposal will utilize in vivo and in vitro wound healing
assays and advanced bioinformatics techniques. Aim 1 will assess how the loss of MFAP5 affects wound
healing, including scar collagen content and architecture, wound breaking strength, myofibroblast activation,
angiogenesis, and wound closure. Single-cell RNA sequencing will be used to identify the FB subpopulation
that produces MFAP5 during wound healing. Aim 2 will examine how MFAP5 influences FB function and gene
expression by utilizing in vitro wound healing assays as well as bulk RNA-sequencing and functional pathway
analysis. Together, the Aims will lead to a better understanding of the importance of MFAP5 in healing skin
wounds and scar formation. Information gained from the proposed research may lead to the development of
novel therapeutics and/or discovery of a prognostic biomarker for treatment of fibrotic diseases.
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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Chen Han其他文献
Ultrawideband microwave photonic filter with high Q-factor using a semiconductor optical amplifier
使用半导体光放大器的具有高品质因数的超宽带微波光子滤波器
- DOI:
- 发表时间:
2017 - 期刊:
- 影响因子:3.6
- 作者:
Chen Han - 通讯作者:
Chen Han
Chen Han的其他文献
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