Supplement: Keratinocyte Galvanotaxis and Wound Healing

描述(由申请人提供)： 这项对美国国立卫生研究院AR44518“趋化电流和伤口愈合”的补充将使用DNA微阵列技术来研究在伤口愈合过程中电刺激诱导的基因表达的变化。外加电场形式的电刺激在临床上用于治疗骨和软组织伤口。由于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的报销，这种疗法的使用频率也越来越高。然而，调节这种方法有效性的分子机制背后的知识仍然缺乏。母基金旨在描述施加直流电场引导人类皮肤角质形成细胞迁移(趋化电流)的信号转导机制。本补充资料扩大了家长拨款的范围，以包括施加直流场对皮肤和表皮组织的影响。提出的策略是利用培养的角质形成细胞和成纤维细胞来设计表皮、真皮或复合皮肤等效组织，并将这些生物工程组织用于伤口愈合的模型中。生物工程组织的使用赋予了在测试模型中限制遗传变异性的优势，允许更容易地检测到由创伤引起的基因表达变化，以及随后通过施加直流电场引起的基因表达变化。该提案提供了一个独特的调查团队，其中包括在临床伤口愈合、组织工程和研究皮肤电刺激效应方面拥有专业知识的PI，以及在大数据集的生物信息学和分析方面拥有独特专业知识的联合调查员Robert Rice教授和David Rocke教授，前者是角质形成细胞生物学方面的公认专家，也是加州大学戴维斯分校DNA微阵列设施的主任。结合他们独特的专业知识和资源，将重点放在已经在操作的调节人类皮肤伤口愈合的模型中的基因表达问题上，为获得对这一过程的新见解提供了强大的协同潜力。这一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.