The Role of microRNAs in Cutaneous Wound Healing

MicroRNAs (miRNAs) are abundant class of noncooding RNAs, typically 21-25 nucleotides in length that are often evolutionarily conserved in metazoans and expressed in a cell and tissue specific manner. Their binding to the 3’UTR of target mRNAs influences the translation or stability of the transcripts. miRNAs play a key role in skin mophogenesis. Recent finding support miRNA involved in hair follicle morphogenesis and skin renewing. In addition, the role of miRNAs was also proposed in a specific phase of the cutaneous wound healing process. Wound healing proceeds through stages of proliferation and tissue remodeling. Repair of damaged human skin is a physiological process involving three overlapping phases “inflammation, proliferation and maturation”. During these different phases, numerous of factors will be needed to act as stimulator for some cellular activity which is required for repairing the skin such as cell matrix production and cell proliferation. Among these factors , hypoxia induced factor 1a (HIF-1and vascular endothelial growth factors (VEGF) play key roles in wound healing by stimulating angiogenesis or cell proliferation which can help the damaged tissue re-acquired the nutrient and oxygen, also regenerate keratinocyte or fibroblast for the loss during the skin damage. Numerous miRNAs be supposed are involving in the gene regulation process before cell dividing or growth factors production. At present, the significance of miRNAs in cutaneous wound healing remains unclear. To clarify the roles of miRNAs in the repairing process can help to understand the real mechanisms of skin repair and maybe can also support how to dealing with the failure of wound recovering. To explore the possible role of miRNAs, we propose a three year study to validate the role of miRNAs in cutaneous wound healing. The aims of this three-year project have been described below. Specific aims of 1st year: (1)To compare the miRNAs expression pattern between normal and wounded skin by miRNA arrays. (2) To test the miRNAs and its potential targets by in vitro repaid screening system. Specific aims of 2d year: To conform the relationship between miRNAs and its targets, also the physiological role of miRNAs by wound healing and angiogenesis assay. Specific aims of 3rd year: DM rate model will be used to test the results which we got from the first two years study. We will try to know whether these miRNAs and targets are key factors for the delay of wound healing.