MicroRNA regulation of the injury response in oral mucosa

MicroRNA对口腔粘膜损伤反应的调节

• 批准号: 9090355
• 负责人: LUISA A DIPIETRO
• 金额: $ 23.98万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-06 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9090355
• 关键词: Affect; Area; Bioinformatics; Biometry; Cell physiology; Cells; Cicatrix; Clinical; Code; Data; Down-Regulation; Epigenetic Process; Epithelial; Epithelial Cells; Event; Exhibits; Exposure to; Extracellular Matrix; FRAP1 gene; Family member; Functional disorder; Genes; Genomics; Goals; Healed; IGF1R gene; Impaired wound healing; In Vitro; Inflammation; Injury; Knowledge; Laboratories; Lead; Mediator of activation protein; Mesenchymal; Methods; MicroRNAs; Modeling; Molecular; Mucous Membrane; Mus; Nature; Oral cavity; Oral mucous membrane structure; Outcome; Outcome Study; Pathology; Pattern; Phenotype; Play; Process; Proliferating; Proteins; Proto-Oncogene Proteins c-akt; Regulation; Research Design; Role; Signal Transduction; Site; Skin; Stimulus; Testing; Therapeutic; Tissues; United States; Untranslated RNA; Wound Healing; base; cell motility; chronic wound; craniofacial complex; deep sequencing; differential expression; epigenetic regulation; healing; improved; in vitro Assay; in vivo; innovation; laser capture microdissection; novel; prevent; programs; public health relevance; regenerative; repaired; response to injury; skin regeneration; therapeutic miRNA; tissue regeneration; wound

 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.

 描述（由适用提供）：伤口愈合受损是一个重大的临床问题，在美国约有650万人。一种几乎总是很快愈合的组织是口腔的粘膜。尽管皮肤和口腔粘膜具有许多形态学相似性，但与皮肤伤口相比，口腔粘膜伤口愈合更快，感染和疤痕形成更少。与皮肤的细胞相比，来自口腔粘膜暴露的上皮细胞会增加迁移和增殖能力，这表明粘膜修复的改善可能涉及上皮细胞的内在差异。尽管一些实验室（包括我们的小组）已经开始研究有助于口服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）及其对口服粘膜增强伤口愈合的贡献的作用知之甚少。我们假设，与皮肤相比，口服粘膜中的上皮细胞经过遗传编程，以更快，更适当地应对损伤。我们进一步假设皮肤和口服粘膜上皮细胞中存在特定位点特异性的MicroRNA调节剂，并且这些microRNA在组织对损伤的特异性反应中起着重要作用。提出了两个具体目标来检验这一假设。 AIM 1将从配对的口腔粘膜伤口和皮肤伤口中建立上皮细胞的动态microRNA曲线，并定义与口服粘膜中伤口增强的伤口愈合相关的microRNA特征。 AIM 2将评估microRNA对伤口上皮成分的功能贡献。愈合，并将评估通过在体内操纵特定的microRNA，确定增益愈合结果（例如，加速伤口闭合）的可行性。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。该理解的区域具有巨大的潜力，可以提出原始的治疗方法，用于修复和再生颅面复合物的组织，包括皮肤和粘膜。