MATRIX METALLOPROTEINASES IN CUTANEOUS WOUND HEALING

描述：这是来自Welgus博士的竞争性续期申请 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（MMP）。 具体目标是：1）定义矩阵组件， 通过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）确定基质诱导的机制 胶原酶表达，通过鉴定顺式作用启动子元件， 胶原酶5'侧翼区的基因，并确定反式 与这些序列结合并调节基因表达的作用因子 表达; 3）确定因子和基因调控机制 控制溶基质素-1和溶基质素-2的表达， 在体内伤口修复中明显表达， 角质形成细胞群;和4）研究胶原酶和基质溶解素-1 角质形成细胞培养物的皮肤等效模型中的和-2表达 受伤后。

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.