Role of ACLP in dermal wound healing

ACLP 在真皮伤口愈合中的作用

• 批准号: 6653248
• 负责人: MATTHEW D LAYNE
• 金额: $ 12.78万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6653248
• 关键词: DNA binding protein; biopsy; carboxypeptidase; cell differentiation; cell migration; cell proliferation; extracellular matrix proteins; fibroblasts; gel mobility shift assay; gene expression; genetic promoter element; genetically modified animals; immunocytochemistry; molecular cloning; muscle cells; northern blottings; nucleic acid sequence; polymerase chain reaction; protein structure function; protein tyrosine kinase; site directed mutagenesis; skin ulcer; statistics /biometry; transcription factor; vascular smooth muscle; wound healing

DESCRIPTION (Taken from the applicant's abstract): Geriatric, malnourished, and diabetic patients with vascular insufficiencies are at increased risk for the development of non-healing dermal wounds that are associated with high morbidity and sometimes mortality. The objectives of the application are to acquire new skills and knowledge investigating dermal wound healing processes, to gain experience in teaching others, and to achieve the necessary expertise to lead an independent research group. These experiences and training at Brigham and Womens Hospital/Harvard Medical School will incorporate the participation in several structured and research activities ultimately leading to scientific independence. The laboratory encompasses 2,500 square feet of newly renovated space equipped with instruments designed for research in cellular and molecular biology, protein chemistry, animal physiology, and histology. The proposed research will examine the role of an extracellular matrix protein, ACLP (aortic carboxypeptidase-like protein) in dermal wound healing. They generated ACLP-null mice, which spontaneously develop non-healing skin ulcers. They hypothesize that an absence of ACLP may prevent healing of skin wounds by impairing the proliferation, differentiation, or migration of dermal fibroblasts. In Aim 1, they will determine the mechanisms by which an absence of ACLP leads to poor wound healing using histological analysis and in vitro assays. In Aim 2, they will identify specific DNA sequences and transcription factors important for regulating the expression of ACLP in dermeal fibroblasts in vitro using reporter gene assays. ACLP promoter LacZ reporter transgenic mice will be generated to evaluate the transcriptional regulation of ACLP during dermal wound healing in vivo. In Aim 3, they will investigate the biological function of ACLP and its interaction with other extracellular matrix proteins and discoidin domain receptor tyrosine kinases (DDR). A series of ACLP and DDR-deletion mutants will be generated to identify domains important for these interactions. In addition, gain-of-function experiments using recombinant adenovirus that produces ACLP will be performed.

描述（摘自申请人摘要）：老年，营养不良，和