Proteases in the Cornea
角膜中的蛋白酶
基本信息
- 批准号:8013793
- 负责人:
- 金额:$ 32.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-08-01 至 2012-12-31
- 项目状态:已结题
- 来源:
- 关键词:AccidentsAddressAdhesionsAgonistAngiogenesis InhibitorsAngiostatinsAntibodiesApoptosisBindingBiological AssayCaspaseCell CountCell divisionCell physiologyCellsCessation of lifeCharacteristicsChemotaxisCorneaCorneal DiseasesCorneal InjuryCorneal UlcerDataDepositionEnzyme-Linked Immunosorbent AssayEnzymesEpithelialEpithelial CellsExtracellular MatrixFibrinFibrinogenFibroblast Growth Factor 2FibroblastsFibrosisGene ExpressionGoalsGrowth FactorHealedHirudinHirudinsHumanIn Situ Nick-End LabelingLaser In Situ KeratomileusisLasersLeadLiverLungMatrix MetalloproteinasesMediatingMembraneMessenger RNAModelingMusMyofibroblastOperative Surgical ProceduresOrgan Culture TechniquesOryctolagus cuniculusPAR-1 ReceptorPatientsPeptide HydrolasesPeptidesPhenotypePhotorefractive KeratectomyPlasminPlasminogenPlasminogen ActivatorPlasminogen Activator Inhibitor 1Platelet-Derived Growth FactorProceduresProtease InhibitorProtein BiosynthesisProteinase-Activated ReceptorsProteinsProthrombinReceptor ActivationReceptor SignalingReverse Transcriptase Polymerase Chain ReactionRoleSignal PathwayStromal CellsSystemTestingThrombinTimeVisualWestern BlottingWound Healingannexin A5cell motilitychemokinecorneal epitheliumcytokinehealingin vivoin vivo Modelinhibitor/antagonistkeratomileusismigrationresearch studyresponsetherapy developmenttissue regeneration
项目摘要
Lay Description: Wound healing in the cornea is incompletely understood; yet each year thousands of people
elect corrective photorefractive surgery. Identification of mechanisms involved in wound healing will lead to
the development of treatments for patients who do not heal properly. In this proposal, thrombin, a protease
that generates fibrin and regulates cellular processes, will be studied. Scientific Description: The goal of this
application is to test the hypothesis that thrombin is involved in corneal wound healing through cleavage of
protease activated receptors and initiation of signaling pathways. Our preliminary data show the components
required to convert prothrombin to thrombin and protease activated receptors mRNA in the human cornea
and the ability of thrombin to alter corneal stromal cell gene expression and cell division. The thrombin
inhibitor hirudin inhibits corneal epithelial wound healing. The SPECIFIC AIMS of this proposal are: 1) TO
DETERMINE WHETHER THROMBIN CAN REGULATE KNOWN CELLULAR STEPS IN CORNEAL
WOUND HEALING. Cultured corneal epithelial cells, stromal keratocytes,fibroblasts and/or myofibroblasts
treated with thrombin will be assayed for thrombin dependent changes in phenotype, apoptosis, total cell
number, cell division, and migration. 2) TO DETERMINE WHETHER THROMBIN STIMULATES CORNEAL
STROMAL CELL SYNTHESIS OF PROTEINS INVOLVED IN WOUND HEALING. The effect of thrombin on
cytokine, chemokine, growth factor and plasminogen activator system component synthesis will be
determined using real-time RT-PCR to characterize thrombin dependent mRNA changes and ELISA and/or
western blots for changes in protein levels. 3) TO DETERMINE THE MECHANISM OF INDUCTION OF
THROMBIN EFFECTS ON CORNEAL CELL FUNCTION AND GENE EXPRESSION. The mechanism of
thrombin induced changes in cell division of stromal myofibroblasts and stimulation of PAI-1 synthesis will be
determined using thrombin inhibitors, inactivated thrombin, thrombin peptides, agonist and antagonists to
thrombin sensitive protease activated receptors and signaling pathway inhibitors. 4) TO DETERMINE
WHETHER THROMBIN AND PAR-1 ARE IMPORTANT FOR CORNEAL WOUND HEALING IN VIVO AND
IN ORGAN CULTURE. Rabbit and human organ culture models and an in vivo model using normal and
PAR-1 deficient mice will be used for these studies.
外行描述:角膜的伤口愈合还不完全清楚;然而,每年有成千上万的人
选择矫正屈光手术。确定涉及伤口愈合的机制将导致
为不能正常愈合的病人开发治疗方法。在这项提案中,凝血酶,一种蛋白酶,
产生纤维蛋白和调节细胞过程的蛋白质,将被研究。科学描述:这一目标
本申请的目的是检验以下假设:凝血酶通过切割角膜基质而参与角膜伤口愈合。
蛋白酶激活受体和信号传导途径的启动。我们的初步数据显示
在人角膜中将凝血酶原转化为凝血酶和蛋白酶激活受体mRNA所需
以及凝血酶改变角膜基质细胞基因表达和细胞分裂的能力。凝血酶
水蛭素抑制剂抑制角膜上皮创伤愈合。本提案的具体目标是:1)
确定凝血酶是否能调节已知的角膜细胞步骤
伤口愈合。培养的角膜上皮细胞、基质角膜细胞、成纤维细胞和/或肌成纤维细胞
将测定用凝血酶处理的细胞的表型、细胞凋亡、总细胞中的凝血酶依赖性变化
细胞分裂和迁移。2)凝血酶是否刺激角膜
基质细胞合成参与伤口愈合的蛋白质。凝血酶对
细胞因子、趋化因子、生长因子和纤溶酶原激活物系统组分的合成将是
使用实时RT-PCR来表征凝血酶依赖性mRNA变化和ELISA来测定,和/或
蛋白质印迹检测蛋白质水平的变化。3)为了确定诱导的机制,
凝血酶对角膜细胞功能和基因表达的影响。的机理
凝血酶诱导的间质肌成纤维细胞分裂的变化和派-1合成的刺激将被认为是
使用凝血酶抑制剂、灭活凝血酶、凝血酶肽、激动剂和拮抗剂测定,
凝血酶敏感蛋白酶激活受体和信号传导途径抑制剂。4)以确定
凝血酶和PAR-1是否对体内角膜伤口愈合重要,
器官培养。兔和人器官培养模型以及使用正常和
PAR-1缺陷小鼠将用于这些研究。
项目成果
期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Focus on molecules: maspin.
- DOI:10.1016/j.exer.2009.07.003
- 发表时间:2010-01
- 期刊:
- 影响因子:3.4
- 作者:Narayan, Malathi;Twining, Sally
- 通讯作者:Twining, Sally
Specific conformational changes of plasminogen induced by chloride ions, 6-aminohexanoic acid and benzamidine, but not the overall openness of plasminogen regulate, production of biologically active angiostatins.
由氯离子、6-氨基己酸和苯甲脒诱导的纤溶酶原的特定构象变化,但不是纤溶酶原的整体开放性,调节生物活性血管抑制素的产生。
- DOI:10.1042/bj20050907
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:Warejcka,DebraJ;Twining,SallyS
- 通讯作者:Twining,SallyS
Maspin increases extracellular plasminogen activator activity associated with corneal fibroblasts and myofibroblasts.
- DOI:10.1016/j.exer.2011.07.008
- 发表时间:2011-11
- 期刊:
- 影响因子:3.4
- 作者:Warejcka, Debra J.;Narayan, Malathi;Twining, Sally S.
- 通讯作者:Twining, Sally S.
Differential conversion of plasminogen to angiostatin by human corneal cell populations.
人角膜细胞群将纤溶酶原差异转化为血管抑制素。
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:2.2
- 作者:Warejcka,DebraJ;Vaughan,KimberlyA;Bernstein,AudreyM;Twining,SallyS
- 通讯作者:Twining,SallyS
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Sally S. Twining其他文献
Large scale separation of protease inhibitors from malignant human breast tissue
- DOI:
10.1007/bf00280275 - 发表时间:
1977-01-01 - 期刊:
- 影响因子:3.700
- 作者:
Sally S. Twining;Arthur S. Brecher - 通讯作者:
Arthur S. Brecher
Genetic control of immune response to sperm whale myoglobin in mice. II. T lymphocyte proliferative response to the synthetic antigenic sites.
小鼠抹香鲸肌红蛋白免疫反应的基因控制。
- DOI:
- 发表时间:
1979 - 期刊:
- 影响因子:4.4
- 作者:
K. Okuda;Sally S. Twining;C. David;M. Atassi - 通讯作者:
M. Atassi
Genetic control of the immune response to myoglobin. V. Analysis of the cross-reactivity of 12 myoglobins with sperm-whale myoglobin antisera of inbred mouse strains in terms of substitutions in the antigenic sites and in the environmental residues of the sites.
对肌红蛋白免疫反应的遗传控制。
- DOI:
- 发表时间:
1981 - 期刊:
- 影响因子:0
- 作者:
M. Atassi;Sally S. Twining;Hermann Lehmann;C. David - 通讯作者:
C. David
The antibody response to myoglobin is independent of the immunized species. Analysis in terms of replacements in the antigenic sites and in environmental residues of the cross-reactions of fifteen myoglobins with sperm-whale myoglobin antisera raised in different species.
对肌红蛋白的抗体反应与免疫物种无关。
- DOI:
- 发表时间:
1980 - 期刊:
- 影响因子:4.1
- 作者:
Sally S. Twining;Hermann LEHMANNt;M. Atassi - 通讯作者:
M. Atassi
Sally S. Twining的其他文献
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{{ truncateString('Sally S. Twining', 18)}}的其他基金
Effect of Maspin on Corneal Heme-and lymph- angiogenesis
Maspin 对角膜血红素和淋巴管生成的影响
- 批准号:
8303225 - 财政年份:2011
- 资助金额:
$ 32.4万 - 项目类别:
Effect of Maspin on Corneal Heme-and lymph- angiogenesis
Maspin 对角膜血红素和淋巴管生成的影响
- 批准号:
8500301 - 财政年份:2011
- 资助金额:
$ 32.4万 - 项目类别:
Effect of Maspin on Corneal Heme-and lymph- angiogenesis
Maspin 对角膜血红素和淋巴管生成的影响
- 批准号:
8187367 - 财政年份:2011
- 资助金额:
$ 32.4万 - 项目类别:
Effect of Maspin on Corneal Heme-and lymph- angiogenesis
Maspin 对角膜血红素和淋巴管生成的影响
- 批准号:
8669978 - 财政年份:2011
- 资助金额:
$ 32.4万 - 项目类别:
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