NRF2 Activation in Diabetic Wound Healing
NRF2 激活在糖尿病伤口愈合中的作用
基本信息
- 批准号:10386811
- 负责人:
- 金额:$ 5.18万
- 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:2021-04-16 至 2026-04-15
- 项目状态:未结题
- 来源:
- 关键词:AmputationAntioxidantsAutomobile DrivingBasement membraneBindingBiological AssayBiological ModelsBlood VesselsCellsChronicCollagenComplicationDataDefectDevelopmentDiabetes MellitusDiabetic NeuropathiesDiabetic mouseEconomic BurdenEquilibriumExhibitsGene ExpressionGenesGenomicsGoalsHistologicHumanHydrogen PeroxideImpaired healingImpaired wound healingImpairmentIn VitroInflammationInvestigationLeadLeg UlcerLifeLipid PeroxidesLower ExtremityMeasuresMedicalMethodsMorbidity - disease rateMusNeuropathyOutcomeOxidative StressPathologyPathway AnalysisPathway interactionsPatientsPharmaceutical PreparationsPharmacotherapyPhenotypePreventionProcessResearchRoleSavingsSkinSolubilitySpecificitySuperoxide DismutaseTestingTimeTissuesTopical applicationVascular DiseasesWorkWound healing therapyactivating transcription factorangiogenesiscatalasechronic ulcerchronic wounddb/db mousediabetes managementdiabeticdiabetic patientdiabetic ulcerdiabetic wound healingexperimental studyhealingimprovedin vivoin vivo Modelinnovationinsightmacrophagemortalitynon-diabeticnon-healing woundsnovelnuclear factor-erythroid 2responserestorationsmall moleculesocialtooltranscription factortranscriptometranscriptome sequencingtreatment effectwoundwound closurewound healingwound treatment
项目摘要
PROJECT SUMMARY / ABSTRACT
For patients with diabetes mellitus (DM), the development of chronic wounds is a life-threatening complication
that necessitates over 100,000 lower extremity amputations per year in the U.S. alone. Despite improvements
in the management of DM, the treatment of diabetic wounds remains challenging due to the inherent defects in
wound healing in diabetic vs. normal skin. Underlying vasculopathies, neuropathies, increased inflammation,
and thickened basement membranes due to diabetes predispose the skin to developing non-healing wounds.
Moreover, diabetic skin exhibits increased oxidative stress and decreased expression of nuclear factor erythroid
2–related factor 2 (NRF2), a transcription factor that activates a pathway that protects cells from increased
oxidative stress. Several studies suggest that NRF2 activation could be a relevant target for the management
and prevention of chronic diabetic wounds. The current proposal utilizes novel small molecule NRF2 activators
that exhibit increased specificity of binding and decreased mutagenicity relative to existing compounds,
without sacrificing solubility, potency, or stability. These novel molecules are an innovative and optimal tool to
study the effects of NRF2 activation on diabetic skin. The long-term objective of this work is to develop
topically-applied NRF2-activating drugs for the treatment of human chronic diabetic wounds.
The goals of the current research are to test the ability of highly specific and novel NRF2
activators to improve diabetic wound healing and to understand their mechanisms of action. In
this study, the effects of NRF2 activation on diabetic wound healing will be investigated in db/db mice, a well-
characterized in vivo model system of DM. Aim 1A will determine the effects of this novel class of NRF2
activators on wound healing, including wound closure, oxidative stress, and the quality of tissue restoration.
Aim 1B will employ whole-tissue RNA-sequencing and functional pathway analysis to investigate the effects of
NRF2 activation in diabetic wounds at the transcriptome level. The data will be used to determine which
functional pathways regulated by NRF2 are important to diabetic skin pathology. Aim 2 will examine the
effects of our candidate molecules on macrophages and investigate whether these novel NRF2 activators act by
improving macrophage function in diabetic wound healing. Investigation into the effects of NRF2 activation on
diabetic wound healing may lead to the development of a life-saving, effective, and practical drug for patients
with chronic diabetic wounds.
项目总结/摘要
对于糖尿病(DM)患者,慢性伤口的发展是威胁生命的并发症
仅在美国每年就有超过10万例下肢截肢手术。尽管有所改善
在糖尿病的管理中,糖尿病伤口的治疗仍然具有挑战性,这是由于
糖尿病患者与正常皮肤的伤口愈合。基础血管病变、神经病变、炎症增加,
以及由于糖尿病而增厚的基底膜使皮肤易于形成不愈合的伤口。
此外,糖尿病皮肤表现出增加的氧化应激和减少的核因子红细胞表达
2-相关因子2(NRF 2),一种激活保护细胞免受增加的细胞凋亡的途径的转录因子。
氧化应激几项研究表明,NRF 2激活可能是一个相关的目标,为管理
和预防慢性糖尿病伤口。目前的建议利用新的小分子NRF 2激活剂
其相对于现有化合物表现出增加的结合特异性和降低的致突变性,
而不牺牲溶解度、效力或稳定性。这些新型分子是一种创新和最佳的工具,
研究NRF 2激活对糖尿病皮肤的影响。这项工作的长期目标是发展
用于治疗人慢性糖尿病伤口的局部施用的NRF 2活化药物。
目前研究的目的是测试高度特异性和新颖的NRF 2
活化剂,以改善糖尿病伤口愈合,并了解其作用机制。在
本研究将在db/db小鼠中研究NRF 2活化对糖尿病伤口愈合的影响,
在DM的体内模型系统中表征。目的1A将确定这种新型NRF 2的作用
在伤口愈合,包括伤口闭合,氧化应激和组织恢复的质量的活化剂。
目的1B将采用全组织RNA测序和功能途径分析来研究
转录组水平上糖尿病伤口中的NRF 2活化。这些数据将用于确定
由NRF 2调节的功能途径对糖尿病皮肤病理学是重要的。目标2将审查
我们的候选分子对巨噬细胞的影响,并研究这些新的NRF 2激活剂是否通过
改善糖尿病伤口愈合中的巨噬细胞功能。研究NRF 2激活对人乳腺癌细胞的影响。
糖尿病伤口愈合可能会导致开发一种挽救生命的,有效的,实用的药物,
患有慢性糖尿病伤口。
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 }}
May Barakat其他文献
May Barakat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 }}
{{ truncateString('May Barakat', 18)}}的其他基金
NRF2 Activation in Diabetic Wound Healing
NRF2 激活在糖尿病伤口愈合中的作用
- 批准号:
10612737 - 财政年份:2021
- 资助金额:
$ 5.18万 - 项目类别:
相似海外基金
Enhancing gamete cryoprotective properties of graphene oxide by dual functionalization with antioxidants and non-penetrating cryoprotectant molecules
通过抗氧化剂和非渗透性冷冻保护剂分子的双重功能化增强氧化石墨烯的配子冷冻保护特性
- 批准号:
24K18002 - 财政年份:2024
- 资助金额:
$ 5.18万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
SBIR Phase I: Sustainable antioxidants for industrial process fluids
SBIR 第一阶段:工业过程流体的可持续抗氧化剂
- 批准号:
2222215 - 财政年份:2023
- 资助金额:
$ 5.18万 - 项目类别:
Standard Grant
Development of a new bone augmentation method that enables long-term survival and long-term functional expression of transplanted cells by antioxidants
开发一种新的骨增强方法,通过抗氧化剂使移植细胞能够长期存活和长期功能表达
- 批准号:
23K09272 - 财政年份:2023
- 资助金额:
$ 5.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Non-Invasive Probing Cellular Oxidative Stress and Antioxidants Therapeutic Effectiveness
非侵入性探测细胞氧化应激和抗氧化剂的治疗效果
- 批准号:
10652764 - 财政年份:2023
- 资助金额:
$ 5.18万 - 项目类别:
Mitochondria-targeting Novel Cationic Hydrazone Antioxidants for the Treatment of Preeclampsia
线粒体靶向新型阳离子腙抗氧化剂用于治疗先兆子痫
- 批准号:
10730652 - 财政年份:2023
- 资助金额:
$ 5.18万 - 项目类别:
Effects of different doses of antioxidants(Vitamin E) intake on exercise induced oxidative stress, antioxidative capacity and chronic inflammation
不同剂量抗氧化剂(维生素E)摄入对运动引起的氧化应激、抗氧化能力和慢性炎症的影响
- 批准号:
22K11609 - 财政年份:2022
- 资助金额:
$ 5.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Contribution of antioxidants to regeneration of rotator cuff insertion
抗氧化剂对肩袖插入再生的贡献
- 批准号:
22K16720 - 财政年份:2022
- 资助金额:
$ 5.18万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Latent Antioxidants for Environmentally Responsible Polymer Formulations
用于环保聚合物配方的潜在抗氧化剂
- 批准号:
RGPIN-2018-04107 - 财政年份:2022
- 资助金额:
$ 5.18万 - 项目类别:
Discovery Grants Program - Individual
Polyunsaturated fatty acid (PUFA), inflammation and antioxidants
多不饱和脂肪酸 (PUFA)、炎症和抗氧化剂
- 批准号:
RGPIN-2019-05674 - 财政年份:2022
- 资助金额:
$ 5.18万 - 项目类别:
Discovery Grants Program - Individual
Suppressed methemoglobin formation of artificial red cell by liposomal antioxidants and its mechanism.
脂质体抗氧化剂抑制人工红细胞高铁血红蛋白形成及其机制
- 批准号:
22K12824 - 财政年份:2022
- 资助金额:
$ 5.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)