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

胶原蛋白 XII 在角膜基质结构和功能的建立以及损伤后重建中的调节作用

• 批准号: 9789325
• 负责人: Edgar Mauricio Espana
• 金额: $ 37.38万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789325
• 关键词: Address; Adult; Americas; Anterior; Apoptosis; Biomechanics; Blindness; Chemical Injury; Cicatrix; Collagen; Cornea; Corneal Injury; Corneal Stroma; Coupled; Data; Deposition; Deterioration; Development; Disease; Environment; Extracellular Matrix; Foundations; Gender; Goals; Homeostasis; Human; Injections; Injury; Keratitis; Keratoplasty; Knockout Mice; Laceration; Mediating; Medical; Modeling; Mus; Myofibroblast; Natural regeneration; Operative Surgical Procedures; Patients; Pattern; Pharmacologic Substance; Phase; Preventive Intervention; Regulation; Role; Secondary to; Stromal Cells; Structure; Testing; Therapeutic Intervention; Thick; Tissue Engineering; Tissues; Transplantation; Traumatic injury; Up-Regulation; Vision; Wound Healing; cell behavior; corneal scar; healing; improved; innovation; insight; interest; light scattering; mouse model; novel; prevent; response; small hairpin RNA; therapeutic development; tissue regeneration; wound

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.

项目总结/文摘