MicroRNA regulation of the injury response in oral mucosa

 描述（由申请人提供）：伤口愈合受损是一个重要的临床问题，在美国影响约650万人。口腔粘膜是一种几乎总是愈合得特别快的组织。虽然皮肤和口腔粘膜具有许多形态学相似性，但口腔粘膜伤口比皮肤伤口愈合更快，并且显示出更少的炎症和瘢痕形成。与皮肤细胞相比，口腔粘膜上皮细胞的迁移和增殖能力增加，表明粘膜修复的改善可能涉及上皮细胞的内在差异。虽然一些实验室（包括我们的小组）已经开始研究有助于口腔粘膜这种特殊愈合能力的分子机制，但大多数努力都集中在蛋白质编码基因上。关于非编码基因（例如microRNA）的作用及其对口腔粘膜伤口愈合的促进作用知之甚少。我们假设，与皮肤相比，口腔粘膜上皮细胞的遗传程序更迅速，更适当地响应损伤。我们假设口腔粘膜上皮细胞的遗传程序更迅速，更适当地响应损伤。我们进一步假设，在皮肤和口腔粘膜上皮细胞中存在位点特异性microRNA调节剂，并且这些microRNA在组织特异性损伤反应中发挥重要作用。提出了两个具体目标来检验这一假设。目的1将建立来自成对口腔粘膜伤口和皮肤伤口的上皮细胞的动态microRNA谱，并将定义与口腔粘膜中增强的伤口愈合相关的microRNA特征。目的2将评估微小RNA对伤口愈合的上皮成分的功能贡献，并将评估调节伤口愈合结果的可行性（例如，加速伤口闭合）。这些研究旨在提供有关microRNA如何促进不同组织中不同愈合动力学的新信息。这个未充分研究的领域有很大的潜力，建议原始的治疗方法，修复和再生的组织颅面复合体，包括皮肤和粘膜。

 DESCRIPTION (provided by applicant): Impaired wound healing is a significant clinical problem, and affects approximately 6.5 million people in the United States. One tissue that nearly always heals exceptionally quickly is the mucosa of the oral cavity. While skin and oral mucosa share many morphological similarities, oral mucosal wounds heal more rapidly and display less inflammation and scar formation than skin wounds. Epithelial cells from oral mucosa exhibit increased migratory and proliferative capacities when compared to cells from skin, suggesting that the improved repair of mucosa may involve intrinsic differences in epithelial cells. While a few laboratories (including our group) have started to investigate the molecular mechanisms that contribute to this exceptional healing capability of oral mucosa, most efforts are focused on protein coding genes. Little is known about the role of non-coding genes (e.g. microRNA) and their contribution to the enhanced wound healing in oral mucosa. We hypothesize that, when compared to skin, epithelial cells in oral mucosa are genetically programmed to more rapidly and appropriately respond to injury. We hypothesize that epithelial cells in oral mucosa are genetically programmed to more rapidly and appropriately respond to injury. We further hypothesize that site-specific microRNA regulators exist in the skin and oral mucosal epithelial cells, and that these microRNAs play an important role in the tissue specific response to injury. Two specific aims are proposed to test this hypothesis. Aim 1 will establish the dynamic microRNA profiles of epithelial cells from paired oral mucosal wounds and skin wounds, and will define the microRNA signature that is associated with enhanced wound healing in oral mucosa. Aim 2 will assess the functional contribution of microRNA to the epithelial component of wound healing, and will evaluate the feasibility of regulating wound healing outcomes (e.g., accelerating wound closure) by manipulating specific microRNAs in vivo. These studies are designed to provide novel information about how microRNAs contribute to the different healing dynamics in different tissues. This understudied area has great potential to suggest original therapeutic approaches for the repair and regeneration of tissues of the craniofacial complex, including skin and mucosa.