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.
项目概要
该申请提出了一个定制的研究培训计划,旨在促进该领域的发展
申请人成为独立调查员。该计划包括生物信息学和
实验室实验,以及量身定制的专业和职业发展机会。培训内容
该计划得到了伊利诺伊大学芝加哥分校当地和机构资源的支持。拟议的
研究将检查控制疤痕形成的机制,这是愈合反应的常见结果。在
成年人,伤口修复的结果几乎总是由杂乱的细胞外物质组成的纤维疤痕
矩阵(ECM)。尽管疤痕形成的调节很复杂,但一个关键特征是成纤维细胞 (FB) 激活,
它产生 ECM 和收缩力。许多组织中都会出现疤痕和纤维化,并可能导致
受影响的器官系统明显受损。我们实验室最近的研究发现了一种新型 FB
在可能与疤痕形成有关的伤口中发挥作用。这些研究表明,伤口 FB 可以充当非
专业吞噬细胞并吞噬凋亡细胞。凋亡细胞吞噬后,FBs 形成纤维化
具有增强迁移、增加收缩性(α-SMA 表达)和增加胶原蛋白的表型
合成。发现纤维化吞噬 FB 中显着上调的一个因素是微纤维相关的
蛋白 5(MFAP5 或微原纤维相关糖蛋白 2/MAGP2)。 MFAP5 影响微纤维功能
可以调节细胞信号通路。有趣的是,MFAP5 与多种人类的纤维化有关
疾病,包括一些癌症和纤维化疾病。尽管如此,人们对其在伤口愈合中的作用仍知之甚少
和疤痕形成。因此,本研究的目的是更好地了解 MFAP5 的功能
皮肤愈合和疤痕形成。我们假设 MFAP5 在皮肤伤口愈合过程中上调
改变 FB 反应并促进疤痕形成。在这项研究中,MFAP5 在伤口愈合中的作用
将在 Mfap5-/- 小鼠(一种成熟的 Mfap5 敲除小鼠系)中进行研究。 MFAP5对的影响
FB表型将在体外进一步研究。该提案将利用体内和体外伤口愈合
分析和先进的生物信息学技术。目标 1 将评估 MFAP5 的丢失如何影响伤口
愈合,包括疤痕胶原蛋白含量和结构、伤口断裂强度、肌成纤维细胞活化、
血管生成和伤口闭合。单细胞 RNA 测序将用于鉴定 FB 亚群
在伤口愈合过程中产生 MFAP5。目标 2 将研究 MFAP5 如何影响 FB 功能和基因
利用体外伤口愈合测定以及批量 RNA 测序和功能途径进行表达
分析。这些目标将共同促进人们更好地了解 MFAP5 在治愈皮肤方面的重要性
伤口和疤痕形成。从拟议的研究中获得的信息可能会导致开发
用于治疗纤维化疾病的新疗法和/或预后生物标志物的发现。
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 }}
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
{{
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 }}
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 5.27万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 5.27万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 5.27万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 5.27万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 5.27万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 5.27万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 5.27万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 5.27万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 5.27万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 5.27万 - 项目类别:
Studentship