Molecular Mechanisms of corneal wound repair
角膜伤口修复的分子机制
基本信息
- 批准号:10674734
- 负责人:
- 金额:$ 41.25万
- 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:2021-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsAdaptor Signaling ProteinAffectAgonistAreaBasement membraneBiochemicalBiologicalBiological AssayBlindnessBlood-Retinal BarrierCell ShapeCellsCentral Nervous SystemCommunicationComplexCorneaCorneal InjuryCytoskeletal ModelingCytoskeletonDataDefectDiabetes MellitusDiabetic mouseDiffuseEndocytosisEpithelial CellsEpitheliumEventEyeFocal AdhesionsGoalsHealthHomeostasisImpaired wound healingImpairmentIn VitroInflammationInjuryIonsLigationMediatingMediatorMedical Care CostsMethodologyMicrovascular DysfunctionModelingMolecularMusNon-Insulin-Dependent Diabetes MellitusOrganizational ChangePainPathogenesisPathologyPersonsPlayProcessProteinsQuality of lifeReactionRecurrenceRegulationReportingResearch PersonnelRiskRoleSignal TransductionStainsSurfaceTechnologyTherapeuticTissuesTractionType 2 diabeticTyrosine PhosphorylationVisionWorld Health Organizationantagonistcell motilitycorneal epithelial wound healingcorneal epitheliumdiabeticdiabetic ulcerdiabetic wound healingepithelial injuryepithelial repairepithelial woundhealingimprovedlive cell imagingmechanotransductionmembermouse modelnon-diabeticpainful neuropathyprotein degradationprotein expressionresponseresponse to injurysensorwoundwound healing
项目摘要
According to the World Health Organization, type 2 diabetes is one of the leading pathologies that
increases the risk of improper wound healing and is now considered to be one of the leading causes of
preventable blindness. Upon injury, adjacent epithelial cells at the wound edge must communicate and
coordinate their response to move forward. Our goal in this proposal is to examine if the interactions
between P2X7 and pannexin1 are critical for homeostasis and wound repair. We have evidence that
pannexin1 mediates P2X7-induced communication and cell motility. These 2 proteins are critical for ion
mobilization, ATP transport and signaling complexes that play roles in inflammation and pain. Other
investigators have shown that P2X7 has a role in the pathogenesis of type 2 diabetes including
microvascular complications, impaired blood retinal barrier and neuropathic pain (Solini and Novak (2019).
We and our collaborators have demonstrated in corneal epithelium that: 1. P2X7 and pannexin1
localization changes with injury and is enhanced near the leading edge of control corneas; 2. Inhibition of
P2X7 diminishes communication between cells, alters components of motility and alters tyrosine
phosphorylation of focal adhesion and adaptor proteins; 4. P2X7 and pannexin1 interact in vitro and we
have preliminary data demonstrating the interaction of P2X7 and pannexin1 in control mice using proximity
ligation assays; 5. We have preliminary data that there is minimal difference in pannexin1 in unwounded
control and diabetic corneal epithelium; however the response to injury differs; and 6. Inhibition of
pannexin1 impedes cell migration in control corneas and in vitro. These led us to hypothesize that P2X7-
pannexin1 interaction in corneal epithelium is required for effective cell-cell communication and signaling
in response to injury and is needed to regulate the cytoskeleton and forces required for cell motility. The
specific aims that we will address are: determine how changes in association of purinoreceptors and
pannexin1 are regulated during corneal wound healing; determine if inhibition and/or activation of these 2
proteins changes the organization of the actin cytoskeleton and cell motility and determine if wound healing
and motility is mediated by a force exerted through the pannexin-P2X7 interaction and if it is affected by
substrate stiffness.
Our data suggest the potential for therapeutic approaches to treat delayed corneal epithelial would healing,
and recurrent corneal erosions in type 2 diabetes.
根据世界卫生组织的数据,2型糖尿病是人类最主要的疾病之一
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Age Dependent Changes in Corneal Epithelial Cell Signaling.
- DOI:10.3389/fcell.2022.886721
- 发表时间:2022
- 期刊:
- 影响因子:5.5
- 作者:
- 通讯作者:
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Vickery E Trinkaus-Randall其他文献
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{{ truncateString('Vickery E Trinkaus-Randall', 18)}}的其他基金
Multicellular regulation of corneal wound healing
角膜伤口愈合的多细胞调节
- 批准号:
8975202 - 财政年份:2014
- 资助金额:
$ 41.25万 - 项目类别:
AFM AND MS TO MONITOR FIBRIL FORMATION FROM AMYLOID IG LIGHT CHAINS AND GAGS
AFM 和 MS 监测淀粉样蛋白 IG 轻链和 GaGS 的纤维形成
- 批准号:
8365539 - 财政年份:2011
- 资助金额:
$ 41.25万 - 项目类别:
ENRICHMENT AND DETECTION METHODOLOGIES FOR EGFR PHOSPHOPEPTIDES
EGFR 磷酸肽的富集和检测方法
- 批准号:
8365555 - 财政年份:2011
- 资助金额:
$ 41.25万 - 项目类别:
AFM AND MS TO MONITOR FIBRIL FORMATION FROM AMYLOID IG LIGHT CHAINS AND GAGS
AFM 和 MS 监测淀粉样蛋白 IG 轻链和 GaGS 的纤维形成
- 批准号:
8170907 - 财政年份:2010
- 资助金额:
$ 41.25万 - 项目类别:
ENRICHMENT AND DETECTION METHODOLOGIES FOR EGFR PHOSPHOPEPTIDES
EGFR 磷酸肽的富集和检测方法
- 批准号:
8170926 - 财政年份:2010
- 资助金额:
$ 41.25万 - 项目类别:
ENRICHMENT AND DETECTION METHODOLOGIES FOR EGFR PHOSPHOPEPTIDES
EGFR 磷酸肽的富集和检测方法
- 批准号:
7955962 - 财政年份:2009
- 资助金额:
$ 41.25万 - 项目类别:
AFM AND MS TO MONITOR FIBRIL FORMATION FROM AMYLOID IG LIGHT CHAINS AND GAGS
AFM 和 MS 监测淀粉样蛋白 IG 轻链和 GaGS 的纤维形成
- 批准号:
7955940 - 财政年份:2009
- 资助金额:
$ 41.25万 - 项目类别:
AFM TO MONITOR FIBRIL FORMATION FROM AMYLOID IG LIGHT CHAINS
AFM 监测淀粉样蛋白 IG 轻链的纤维形成
- 批准号:
7723045 - 财政年份:2008
- 资助金额:
$ 41.25万 - 项目类别:














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