COLLAGEN METABOLISM IN WOUND REPAIR

伤口修复中的胶原蛋白代谢

• 批准号: 6628740
• 负责人: IRWIN KELMAN COHEN
• 金额: $ 29.36万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-12-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6628740
• 关键词: RNase protection assay; biopsy; clinical research; collagen; connective tissue metabolism; decubitus ulcer; drug screening /evaluation; elastases; endopeptidases; extracellular matrix; exudate /transudate; fibroblasts; gene expression; growth factor receptors; histochemistry /cytochemistry; human subject; immunologic assay /test; in situ hybridization; inhibitor /antagonist; longitudinal human study; neutrophil; nursing care evaluation; procollagen; proteolysis; tetracyclines; wound healing

DESCRIPTION (Verbatim from the applicant's abstract) Pressure ulcers are one of the most debilitating and costly problems faced by elderly and spinal cord injury patients. Treatment of this growing problem remains empirical. Progress in the development of strategies for improving treatment of pressure ulcers has been hampered greatly by the lack of a fundamental definition of the pressure ulcer microenvironment and the underlying cellular, biochemical, and molecular mechanisms responsible for the poor rate of healing of these lesions. Therefore we have pursued the hypothesis and generated extensive evidence that the chronicity of these lesions is related to the enhanced proteolytic environment associated with an over exuberant presence of polymorphonuclear leukocytes (neutrophils). Neutrophils are the predominant inflammatory cell in pressure ulcers and are a source for a number of proteinases including collagenase (MMP-8) and elastase. Recent findings based on in situ hybridization analyses, indicate that mesenchymal cells in the beds of pressure ulcers contain abundant levels of procollagen transcripts suggesting that these cells are synthetically active. Therefore, the major objective of this project will be to test the hypothesis that the excessive proteolytic environment can be diminished by good wound care and this will be associated with increased collagen matrix accumulation, and restitution of the integrity of key growth factor receptors. In addition, the hypothesis that the synthetic/degradative equilibrium of pressure ulcers can be altered using a therapeutic agent already approved for use in humans will also be tested. A longitudinal characterization of pressure ulcers will include histochemical identification of neutrophils and other cell populations, an assessment of levels and activities of proteinases that are primarily neutrophil-derived, and measurement of levels of specific proteinase inhibitors. Expression of extracellular matrix will be monitored by analyzing collagen synthesis and deposition and the location and levels of procollagen transcripts. Similarly, expression of growth factor receptors will be examined by qualitative and quantitative protein assessment and by in situ hybridization and quantitative ribonuclease protection assay. These data should provide key inforrnation for the development of new strategies for the treatment of pressure ulcers as well as other chronic non-healing wounds.

描述（逐字化申请人摘要）压疮是之一 老年人和脊髓面临的最衰弱和昂贵的问题 受伤患者。对这个日益增长的问题的处理仍然是经验的。进步 在制定改善压力溃疡治疗的策略中 由于缺乏压力的基本定义，受到了极大的阻碍 溃疡微环境以及下面的细胞，生化和分子 导致这些病变愈合率较差的机制。 因此，我们提出了假设，并产生了广泛的证据 这些病变的慢性性与增强的蛋白水解有关 与多形核的过度存在有关的环境 白细胞（中性粒细胞）。中性粒细胞是主要的炎症细胞 压疮，是许多蛋白酶的来源 胶原酶（MMP-8）和弹性酶。最新发现基于原位 杂交分析，表明压力床中的间充质细胞 溃疡含有大量的胶原成绩单，表明这些成绩单 细胞具有合成活性。因此，该项目的主要目标 将是测试过多的蛋白水解环境可以的假设 通过良好的伤口护理减少，这将与增加有关 胶原蛋白基质的积累，并恢复关键增长的完整性 因子受体。另外，合成/降解的假设 已经可以使用治疗剂改变压力溃疡的平衡 批准用于人类的批准也将进行测试。纵向表征 压力溃疡的结构将包括中性粒细胞的组织化学鉴定和 其他细胞种群，评估蛋白酶的水平和活性 主要是嗜中性粒细胞的，并测量特定水平 蛋白酶抑制剂。细胞外基质的表达将通过 分析胶原蛋白合成和沉积以及位置和水平 Procollagen成绩单。同样，生长因子受体的表达将 通过定性和定量蛋白质评估和原位进行检查 杂交和定量核糖核酸酶保护测定法。这些数据应该 为制定新策略提供关键的信息 治疗压疮以及其他慢性非治疗伤口。