Supplement: Keratinocyte Galvanotaxis and Wound Healing

描述（由申请人提供）： NIH资助AR44518“趋电性和伤口愈合”的补充将使用DNA微阵列技术来研究伤口愈合的电刺激诱导的基因表达变化。以施加电场的形式的电刺激在临床上用于愈合骨和软组织伤口。它也被越来越频繁地使用，现在医疗保险和医疗补助服务中心已经批准这种疗法用于治疗慢性皮肤溃疡。然而，缺乏介导这种方法有效性的分子机制背后的知识。母基金旨在描绘信号转导机制，通过该机制施加直流电场指导人类皮肤源性角质形成细胞的迁移（趋电性）。该补充扩展了母公司补助金的范围，以包括应用DC场对真皮和表皮组织的影响。提出的策略是使用培养的角质形成细胞和成纤维细胞工程化表皮、真皮或复合皮肤等效组织，并将这些生物工程化组织用于伤口愈合模型。生物工程组织的使用赋予了限制测试模型中的遗传变异性的优点，从而允许更容易地检测到由创伤以及随后通过施加DC电场诱导的基因表达的变化。 该提案提供了一个独特的研究人员团队，包括在临床伤口愈合，组织工程和研究皮肤电刺激效果方面具有专业知识的PI，以及共同研究员Robert Rice教授，角质形成细胞生物学公认的专家和加州大学戴维斯分校DNA微阵列设施的主任，以及共同研究员大卫洛克教授，图像处理和集成计算中心主任，在生物信息学和大型数据集分析方面拥有独特的专业知识。将他们独特的专业知识和资源结合起来，专注于调节人类皮肤伤口愈合的已运作模型中的基因表达问题，为获得对这一过程的新见解提供了强大的协同潜力。这些知识将为开发新的治疗干预措施以促进伤口修复提供机会。

DESCRIPTION (provided by applicant): This supplement to NIH grant AR44518 "Galvanotaxis and Wound Healing" will use DNA microarray technology to investigate the changes in gene expression induced by electric stimulation of wound healing. Electric stimulation in the form of applied electric fields is used clinically to heal bone and soft tissue wounds. It is also being used with increasing frequency now that the Centers for Medicare and Medicaid Services has approved this therapy for reimbursement for treatment of chronic skin ulcers. Yet the knowledge behind the molecular mechanisms that mediate the effectiveness of this approach is lacking. The parent grant seeks to delineate the signal transduction mechanisms by which applied DC electric fields direct migration (galvanotaxis) in human skin-derived keratinocytes. This supplement extends the scope of the parent grant to include the effects of applied DC fields on dermal as well as epidermal tissues. The strategy propose is to engineer epidermal, dermal or composite skin equivalent tissues using cultured keratinocytes and fibroblast and use these bioengineered tissues in models of wound healing. The use of bioengineered tissues confers the advantage of constraining genetic variability in the test model, allowing the changes in gene expression induced by wounding, and subsequently, by the application of DC electric fields to be more easily detected. The proposal offers a unique team of investigators including the PI who has expertise in clinical wound-healing, tissue engineering and studies the effects of electrical stimulation in skin, and co-investigator Prof. Robert Rice, a recognized expert in keratinocyte biology and director of the UC Davis DNA Microarray Facility, and co-investigator Prof. David Rocke, director of the Center for Image Processing and Integrated Computing, with unique expertise in bioinformatics and analysis of large data sets. Combining their unique expertise and resources to focus on the question of gene expression in an already operational model for modulating human skin wound healing provides powerful synergistic potential for deriving new insights into this process. This knowledge will provide the opportunity to develop novel therapeutic interventions to enhance wound repair.