Understanding the role of VEGF in scar formation
了解 VEGF 在疤痕形成中的作用
基本信息
- 批准号:10437009
- 负责人:
- 金额:$ 20.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAngiogenic FactorApoptosisAreaBehaviorBlood VesselsCellsCicatrixClinicalCollagenComplicationDataDefectDepositionDermalEmbryoEndothelial CellsEstheticsFibroblastsFibrosisGenerationsHealth Care CostsIn VitroInjuryKDR geneKnockout MiceKnowledgeLinkMediator of activation proteinMitogensMusMyofibroblastNutrientOperative Surgical ProceduresOrganOxygenPatientsPlayProcessProductionRegulationRoleSignal TransductionSiteSkinSkin wound healingSurgical incisionsTestingTimeTissuesVEGFA geneVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth FactorsWound modelsangiogenesisbasecell typecombatconditional knockouthealinghigh rewardhigh riskin vivointerestmigrationmouse modelnovelnovel therapeuticspreventpsychosocialreceptorrepairedskin woundtoolwoundwound healing
项目摘要
PROJECT SUMMARY:
Complications in the wound repair process, including the formation of excessive or abnormal scar
formation, affect millions of patients and result in substantial health care costs. Scar tissue impedes normal
skin function and can have severe psychosocial consequences. The ability to limit the amount of scar tissue
that forms following injury or surgical procedures would be a major clinical advance that would have a
tremendous impact on patients. In order to develop novel therapies to combat scarring, a more precise
understanding of the mechanisms that regulate scar formation is needed.
A growing body of evidence is emerging suggesting that the pro-angiogenic growth factor vascular
endothelial growth factor-A (VEGF) promotes scar formation. However, little has been done to dissect the
mechanisms by which VEGF contributes to scarring. Our preliminary data suggest that fibroblasts, the cell type
responsible for scar formation, express VEGF receptors and that cultured fibroblasts respond directly to VEGF.
Therefore, it is possible that in addition to regulating wound angiogenesis, VEGF may also directly stimulate to
scar formation by signaling through VEGFR-1 and/or VEGFR-2 in dermal fibroblasts.
Based on the evidence suggesting that VEGF promotes scar formation as well as preliminary data
suggesting that VEGF receptors are present on dermal fibroblasts and that these cells can respond to VEGF,
the central hypothesis of the proposed studies is that VEGF promotes scar tissue deposition through direct
stimulation of dermal fibroblasts. The following specific aims will be carried out to test this hypothesis: Aim 1 –
Assess the effects of VEGF on fibroblast function in vitro; Aim 2 – Determine the effects of VEGF on fibroblast
function in vivo.
Despite the mounting evidence that VEGF regulates scar formation, no detailed mechanistic studies have
been performed. Here, novel mouse models will be used to address this gap in knowledge by characterizing
direct effects of VEGF on fibroblasts and dissecting the mechanisms by which VEGF promotes scar formation.
The mechanisms identified as a result of these studies could extend beyond wound-induced scar formation,
and have the potential to also play a role in the regulation of fibrosis in the skin as well as other organs.
项目概要:
伤口修复过程中的并发症,包括形成过多或异常的疤痕
的形成,影响数百万患者并导致巨额医疗费用。疤痕组织妨碍正常
皮肤功能,并可能产生严重的心理社会后果。限制疤痕组织数量的能力
受伤或手术后形成的这种疾病将是一项重大的临床进步,将有
对患者影响巨大。为了开发对抗疤痕的新疗法,需要更精确的方法
需要了解调节疤痕形成的机制。
越来越多的证据表明促血管生成生长因子
内皮生长因子-A (VEGF) 促进疤痕形成。然而,几乎没有采取任何措施来剖析
VEGF 导致疤痕形成的机制。我们的初步数据表明,成纤维细胞,细胞类型
负责疤痕形成,表达 VEGF 受体,并且培养的成纤维细胞直接对 VEGF 做出反应。
因此,VEGF除了调节伤口血管生成外,还可能直接刺激
通过真皮成纤维细胞中的 VEGFR-1 和/或 VEGFR-2 信号传导形成疤痕。
基于 VEGF 促进疤痕形成的证据以及初步数据
表明 VEGF 受体存在于真皮成纤维细胞上,并且这些细胞可以对 VEGF 做出反应,
该研究的中心假设是 VEGF 通过直接促进疤痕组织沉积
刺激真皮成纤维细胞。将执行以下具体目标来检验这一假设: 目标 1 –
体外评估VEGF对成纤维细胞功能的影响;目标 2 – 确定 VEGF 对成纤维细胞的影响
在体内发挥作用。
尽管越来越多的证据表明 VEGF 调节疤痕形成,但尚无详细的机制研究
已执行。在这里,新型小鼠模型将用于通过表征来解决这一知识差距
VEGF 对成纤维细胞的直接影响并剖析 VEGF 促进疤痕形成的机制。
这些研究结果确定的机制可能超越伤口引起的疤痕形成,
并且有可能在调节皮肤和其他器官的纤维化中发挥作用。
项目成果
期刊论文数量(0)
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TRACI A WILGUS其他文献
TRACI A WILGUS的其他文献
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{{ truncateString('TRACI A WILGUS', 18)}}的其他基金
Understanding the role of VEGF in scar formation
了解 VEGF 在疤痕形成中的作用
- 批准号:
10303382 - 财政年份:2021
- 资助金额:
$ 20.58万 - 项目类别:
Evaluation of a novel pro-fibrotic regulatory pathway in the skin
皮肤中新型促纤维化调节途径的评估
- 批准号:
9234862 - 财政年份:2017
- 资助金额:
$ 20.58万 - 项目类别:
Interleukin-33 in skin carcinogenesis
Interleukin-33 在皮肤癌发生中的作用
- 批准号:
8638636 - 财政年份:2013
- 资助金额:
$ 20.58万 - 项目类别:
Mast cells and immunosuppression in skin cancer
皮肤癌中的肥大细胞和免疫抑制
- 批准号:
8386406 - 财政年份:2012
- 资助金额:
$ 20.58万 - 项目类别:
Mast cells and immunosuppression in skin cancer
皮肤癌中的肥大细胞和免疫抑制
- 批准号:
8529528 - 财政年份:2012
- 资助金额:
$ 20.58万 - 项目类别:
Keratinocyte responses to vascular endothelial growth factor in carcinogenesis
致癌过程中角质形成细胞对血管内皮生长因子的反应
- 批准号:
7846338 - 财政年份:2009
- 资助金额:
$ 20.58万 - 项目类别:
Keratinocyte responses to vascular endothelial growth factor in carcinogenesis
致癌过程中角质形成细胞对血管内皮生长因子的反应
- 批准号:
7499079 - 财政年份:2007
- 资助金额:
$ 20.58万 - 项目类别:
Keratinocyte responses to vascular endothelial growth factor in carcinogenesis
致癌过程中角质形成细胞对血管内皮生长因子的反应
- 批准号:
8138001 - 财政年份:2007
- 资助金额:
$ 20.58万 - 项目类别:
Keratinocyte responses to vascular endothelial growth factor in carcinogenesis
致癌过程中角质形成细胞对血管内皮生长因子的反应
- 批准号:
7677951 - 财政年份:2007
- 资助金额:
$ 20.58万 - 项目类别:
Keratinocyte responses to vascular endothelial growth factor in carcinogenesis
致癌过程中角质形成细胞对血管内皮生长因子的反应
- 批准号:
7915768 - 财政年份:2007
- 资助金额:
$ 20.58万 - 项目类别:
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