Shilo Shani, Roy Sashwati, Khanna Savita, Sen Chandan K
Laboratory of Molecular Medicine, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio, USA.
DNA Cell Biol. 2007 Apr;26(4):227-37. doi: 10.1089/dna.2006.0568.
Repair of a defect in the human skin is a highly orchestrated physiological process involving numerous factors that act in a temporally resolved synergistic manner to re-establish barrier function by regenerating new skin. The inducible expression and repression of genes represents a key component of this regenerative process. MicroRNAs (miRNAs) are approximately 22-nucleotide-long endogenously expressed non-coding RNAs that regulate the expression of gene products by inhibition of translation and/or transcription in animals. miRNAs play a key role in skin morphogenesis and in regulating angiogenesis. The vascular endothelial growth factor signaling path seems to be under repressor control by miRNAs. Mature miRNA-dependent mechanisms impair angiogenesis in vivo. It is critically important to recognize that the understanding of cutaneous wound healing is incomplete without appreciating the functional significance of wound-induced miRNA. Ongoing work in our laboratory has led to the observation that the cutaneous wound healing process involves changes in the expression of specific miRNA at specific phases of wound healing. We hypothesize that dysregulation of specific miRNA is critical in derailing the healing sequence in chronic problem wounds. If tested positive, this hypothesis is likely to lead to completely novel diagnostic and therapeutic strategies for the treatment of problem wounds.
人类皮肤缺损的修复是一个高度协调的生理过程，涉及众多因素，这些因素以时间上可分辨的协同方式发挥作用，通过再生新皮肤来重新建立屏障功能。基因的诱导表达和抑制是这一再生过程的关键组成部分。微小RNA（miRNA）是长度约为22个核苷酸的内源性表达的非编码RNA，在动物中通过抑制翻译和/或转录来调节基因产物的表达。miRNA在皮肤形态发生和调节血管生成中起关键作用。血管内皮生长因子信号通路似乎受miRNA的抑制控制。成熟的miRNA依赖性机制在体内损害血管生成。必须认识到，如果不了解伤口诱导的miRNA的功能意义，对皮肤伤口愈合的理解就是不完整的。我们实验室正在进行的工作已观察到，皮肤伤口愈合过程涉及伤口愈合特定阶段特定miRNA表达的变化。我们假设特定miRNA的失调在破坏慢性问题伤口的愈合序列中起关键作用。如果测试结果为阳性，这一假设可能会带来治疗问题伤口的全新诊断和治疗策略。
