Regulation of tissue repair and scar formation by the stromal niche

项目描述/摘要 角膜瘢痕形成是一个公共卫生问题，也是角膜移植的常见适应症。 不同病理过程后出现细胞外基质无序沉积或疤痕 包括角膜感染、先天性疾病和创伤。该提案的长期目标是解决 创新概念，即重建一个独特环境或基质生态位， 机械和化学刺激在损伤后对改善瘢痕形成至关重要。了解机制 损伤后直接重建基质功能是治疗干预的潜在目标。我们 初步结果支持这些概念。具体的目的是：（1）阐明胶原V的调节 重新表达在重建角膜基质功能;（2）确定这种独特的作用， 微环境在调节角质形成细胞-成纤维细胞-肌成纤维细胞分化中的作用;以及（3）确定 胶原蛋白V，调节潜在的TGF-β活化，从而调节基质沉积和瘢痕形成。 这项工作将为未来的医疗或手术治疗的发展提供关键信息， 角膜瘢痕形成的患者，并将为角膜基质的治疗操作打开大门。

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.