MATRIX METALLOPROTEINASES IN CUTANEOUS WOUND HEALING

基质金属蛋白酶在皮肤伤口愈合中的作用

• 批准号: 2517434
• 负责人: HOWARD G WELGUS
• 金额: $ 26.39万
• 依托单位: BARNES-JEWISH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2517434
• 关键词: biological signal transduction; collagen disorder; collagenase; connective tissue cells; enzyme activity; enzyme inhibitors; enzyme linked immunosorbent assay; extracellular matrix; gel filtration chromatography; gene expression; genetic regulatory element; genetic transcription; human tissue; in situ hybridization; keratinocyte; laboratory rabbit; metalloendopeptidases; molecular cloning; molecular pathology; skin; stromelysin; tissue /cell culture; transcription factor; wound healing

Description: This is a competitive renewal application from Dr. Welgus to investigate various aspects of the control of collagenase and matrix- metalloproteinase (MMP) production by human keratinocytes in culture. The specific aims are to: 1) define matrix components which induce collagenase production by cultured keratinocytes, identify the cell surface recognition integrins that mediate the induction, and study the signal transduction pathways; 2) define the mechanism of matrix-induced collagenase expression, by identifying cis-acting promoter elements in the collagenase 5' flanking region of the gene, and identify trans acting factors that bind to these sequences and modulate gene expression; 3) determine the factors and gene regulatory mechanisms controlling the expression of stromelysin-1 and stromelysin-2, which are apparently expressed in vivo in wound repair by distinctly different populations of keratinocytes; and 4) study collagenase and stromelysin-1 and -2 expression in a skin-equivalent model of keratinocyte cultures after wounding.

描述：这是来自Welgus博士的竞争性续订申请 为了研究胶原酶和基质控制的各个方面- 培养的人角质形成细胞产生金属蛋白酶。 具体目的是：1)定义导致 培养的角质形成细胞产生胶原酶，鉴定细胞 介导诱导的表面识别整合素，并研究 信号转导途径；2)明确基质诱导的机制 胶原酶表达，通过鉴定顺式作用的启动子元件 胶原酶基因5‘侧翼区，并鉴定反式 与这些序列结合并调节基因的作用因子 3)确定影响基因表达的因素和基因调控机制 控制基质分解素-1和基质分解素-2的表达，这两个因子是 在伤口修复中的体内表达明显不同 角质形成细胞群体；4)胶原酶和基质分解酶-1的研究 角质形成细胞培养的皮肤等效模型中AND-2的表达 在伤人之后。