Regulatory roles for collagen XII in establishment of corneal stromal structure and function and re-establishment after injury

项目总结/摘要 本申请解决了胶原蛋白XII对于角膜上皮细胞的获得是必需的这一一般假设。 间质结构和功能，并用于损伤后的再获取。胶原蛋白XII调节 基质伤口愈合是创新性的，并开启了多种转化前景。注意到瘢痕改善 在没有胶原蛋白XII的情况下伤口愈合期间。我们的总体目标是提供一个基础， 应用于伤口愈合期间的基质沉积操作，并为 旨在促进无瘢痕基质再生的药物和外科治疗干预。的 具体目的是：（1）阐明胶原XII在基质结构获得中的调节作用， 功能;（2）确定胶原蛋白XII调节基质伤口愈合的机制;和（3） 鉴定涉及调节胶原XII以减少人基质瘢痕治疗干预 在伤口愈合期间形成。本研究的目的是检验以下假设：（1）差异性和调节性 胶原蛋白XII的表达是获得基质结构和功能所需的关键机制;（2） 在发育和成熟过程中观察到的胶原XII表达模式在成年过程中重现， 基质伤口愈合以调节基质愈合和瘢痕形成;和（3）下调胶原XII 表达有利于基质再生而不是瘢痕形成。因此，调节胶原蛋白XII的表达， 对正常基质结构和功能的重新获得具有积极影响。该提案将具有 重大影响，为开发新的医疗和外科治疗提供关键信息 对于基质瘢痕患者，迄今为止，前板层和穿透性全瘢痕最常见的适应症 在美国的厚度移植。

PROJECT SUMMARY/ABSTRACT This application addresses the general hypothesis that collagen XII is essential for the acquisition of corneal stroma structure and function, and for reacquisition after injury. The concept that collagen XII modulates stromal wound healing is innovative and opens multiple translational prospects. Scar amelioration is noted during wound healing in the absence of collagen XII. Our overall goal is to provide a foundation to develop applications for matrix deposition manipulation during wound healing, and provide a rational basis for pharmaceutical and surgical therapeutic interventions aimed at promoting scarless stromal regeneration. The specific aims are to: (1) elucidate the regulatory roles of collagen XII in the acquisition of stromal structure and function; (2) determine the mechanism(s) whereby collagen XII regulates stromal wound healing; and (3) identify therapeutic interventions involving modulation of collagen XII to decrease human stromal scar formation during wound healing. The aims will test the hypotheses that: (1) differential and regulated expression of collagen XII is a critical mechanism required for acquisition of stromal structure and function; (2) collagen XII expression patterns observed in development and maturation are recapitulated during adult stromal wound healing to regulate stromal healing and scar formation; and (3) down-regulating collagen XII expression favors stromal regeneration over scarring. Therefore, modulation of collagen XII expression will have a positive impact on the reacquisition of normal stromal structure and function. This proposal will have significant impact, providing critical information for the development of novel medical and surgical therapies for patients with stromal scars, by far the most common indication for anterior lamellar and penetrating full thickness transplantation in America.