Regulation of tissue repair and scar formation by the stromal niche

项目说明/摘要 角膜瘢痕形成是一个公共卫生问题，也是角膜移植非常常见的适应症。 细胞外基质的无序沉积或在不同的病理过程中形成疤痕 包括角膜感染、先天性疾病和创伤。这项提案的长期目标是解决 创新的概念，重建一个独特的环境或基质利基与其独特的 机械和化学提示是关键的创伤后，以改善疤痕。了解相关机制 损伤后间质功能的直接重建是治疗干预的潜在靶点。我们的 初步结果支持这些概念。其具体目的是：(1)阐明V型胶原的调节 重新表达在重建角膜基质功能中的作用；(2)确定这种独特的作用 微环境在调节角质细胞-成纤维细胞-肌成纤维细胞分化中的作用 V型胶原在调节潜在的转化生长因子-β激活，从而调节基质沉积和瘢痕形成中起着重要作用。 这项工作将为未来内科或外科治疗的发展提供重要信息。 对于有角膜疤痕的患者，将为治疗操作角膜基质打开大门。

Project Description/ Abstract Corneal scarring is a public health problem and a very common indication for corneal transplantation. Disorganized deposition of extracellular matrix or scarring occurs after different pathological processes including corneal infections, congenital diseases and trauma. The long term goal of this proposal is to address the innovative concept that reestablishment of a unique environment or stromal niche with its unique mechanical and chemical cues is critical after injury to ameliorate scarring. Understanding the mechanisms that direct reestablishment of stromal function after injury is a potential target for therapuetic interventions. Our preliminary results support these concepts. The specific aims are to: (1) elucidate the regulation of collagen V reexpression in the reestablishment of corneal stroma function; (2) determine the role of this unique microenvironment in regulating keratocyte-fibroblast- myofibroblast differentiation; and (3) determine the roles of collagens V, in regulating latent TGF-β activation and therefore modulating matrix deposition and scarring. This work will provide critical information for the development of future medical or surgical therapies for patients with corneal scarring and will open the door for therapeutic manipulation of the corneal stroma.