Regulation of tissue repair and scar formation by the stromal niche

基质生态位对组织修复和疤痕形成的调节

• 批准号: 10503082
• 负责人: Edgar Mauricio Espana
• 金额: $ 43.31万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10503082
• 关键词: Address; Apoptosis; Area; Blindness; Bromodeoxyuridine; C57BL/6 Mouse; Chemicals; Cicatrix; Clinical; Collagen; Cornea; Corneal Stroma; Cues; Data; Deposition; Development; Disease; Down-Regulation; Environment; Extracellular Matrix; Fibroblasts; Foundations; Functional disorder; Future; Goals; Infection; Injury; Integrin alphaV; Integrins; Intervention; Keratoplasty; Label; Mechanics; Medical; Morbidity - disease rate; Myofibroblast; Natural regeneration; Operative Surgical Procedures; Pathologic Processes; Patients; Peripheral; Phase; Phenotype; Play; Process; Prognosis; Property; Public Health; Regulation; Research; Resistance; Role; Secondary to; Severities; Signal Transduction; Stromal Cells; Structure; Therapeutic; Therapeutic Intervention; Time; Tissues; Transforming Growth Factor beta; Transplantation; Trauma; Vision; Work; base; corneal scar; density; fibrillogenesis; gene therapy; in vivo; in vivo Model; inhibitor; innovation; light scattering; mechanical properties; mechanical signal; mouse model; novel; repaired; response to injury; small hairpin RNA; stem cells; tissue repair; wound; wound healing; wound response

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.

项目描述/摘要 角膜疤痕是一个公共健康问题，也是角膜移植的一个非常常见的适应症。 不同病理过程后会出现细胞外基质无序沉积或疤痕形成 包括角膜感染、先天性疾病和外伤。该提案的长期目标是解决 以其独特的方式重建独特的环境或基质生态位的创新理念 受伤后机械和化学信号对于改善疤痕至关重要。了解机制 损伤后基质功能的直接重建是治疗干预的潜在目标。我们的 初步结果支持这些概念。具体目标是：（1）阐明胶原蛋白V的调控 角膜基质功能重建中的重新表达； (2)确定这个独特的角色 调节角质细胞-成纤维细胞-肌成纤维细胞分化的微环境； (3) 确定角色 V 胶原蛋白，调节潜在的 TGF-β 激活，从而调节基质沉积和疤痕形成。 这项工作将为未来医学或外科疗法的开发提供重要信息 患有角膜疤痕的患者将为角膜基质的治疗操作打开大门。