Selectins and Fetal wound Healing

选择素和胎儿伤口愈合

• 批准号: 6719359
• 负责人: OLUYINKA OLUROTIMI OLUTOYE
• 金额: $ 12.97万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6719359
• 关键词: SCID mouse; adult human (21+); athymic mouse; cell adhesion molecules; cell cell interaction; cell membrane; embryo /fetus; enzyme linked immunosorbent assay; fibrosis; flow cytometry; gene expression; gene targeting; genetically modified animals; immunocytochemistry; inflammation; leukocyte activation /transformation; platelets; protein structure function; scars; selectins; skin disorder; skin transplantation; vascular endothelium; wild animals; wound healing

DESCRIPTION (provided by applicant): The overall objective of this project is to gain an in depth understanding into the role of selectins in the modulation of the inflammatory response following wounding in the adult and fetus. Fetal dermal wound healing is characterized by a scant inflammatory response and minimal fibrosis. Although fetal inflammatory cells are generally considered immature, an acute inflammatory response (with fibrosis) can be evoked at the site of fetal wounds by the application of diverse stimuli. Selectins are cell surface lectin molecules expressed on both leukocytes and endothelial cells that interact with their respective carbohydrate ligands to facilitate the early events of leukocyte recruitment, and thereby, contribute significantly to the inflammatory process. The contributions of these adhesion molecules to wound closure, repair and scar formation are poorly understood. This study is therefore proposed to evaluate the role of selectins in wound healing. The application will be centered on the hypothesis that the minimal inflammation noted in fetal dermal wounds is a consequence of alterations in expression of P- and E-selectin on fetal platelets and endothelial cells. To test this hypothesis, the relative expression of selectins on adult and fetal platelets and endothelial cells will be determined. Mice with targeted deletions of individual or combinations of selectins will be studied to determine the consequences of selectin absence on wound healing. Using the murine syngeneic fetal skin transplantation model and creating mice chimeric for selectins, the specific contributions of platelet or endothelial selectins in the inflammatory response will be elucidated. Understanding the mechanism of scarless fetal wound healing will provide alternative avenues to modulate the postnatal wound healing response. This will have implications not only in the management of complications of dermal wound healing (bum contractures, keloids, hypertrophic scars, non-healing ulcers, etc.) but also in all conditions where fibrosis is an undesired consequence, such as pulmonary fibrosis, strictures, peritoneal adhesions, hepatic fibrosis, etc. Furthermore, understanding how selectins modulate the inflammatory response in the fetus will reveal valuable information that may explain the predisposition of neonates and premature infants to infections. These may then provide opportunities to assist with the inflammatory responses in these children when they are most vulnerable.

描述（由申请人提供）： 该项目的总体目标是深入了解选择素在调节成人和胎儿受伤后炎症反应中的作用。胎儿真皮伤口愈合的特点是很少的炎症反应和最小的纤维化。尽管胎儿炎症细胞通常被认为是不成熟的，但通过施加不同的刺激，可以在胎儿伤口部位引起急性炎症反应（伴有纤维化）。选择素是在白细胞和内皮细胞上表达的细胞表面凝集素分子，其与各自的碳水化合物配体相互作用以促进白细胞募集的早期事件，从而显着促进炎症过程。人们对这些粘附分子对伤口闭合、修复和疤痕形成的贡献知之甚少。因此，建议本研究评估选择素在伤口愈合中的作用。该应用将集中在这样的假设上：胎儿真皮伤口中注意到的最小炎症是胎儿血小板和内皮细胞上 P-和 E-选择素表达改变的结果。为了检验这一假设，将测定成人和胎儿血小板和内皮细胞上选择素的相对表达。将研究靶向删除单个选择素或选择素组合的小鼠，以确定选择素缺失对伤口愈合的影响。使用小鼠同基因胎儿皮肤移植模型并创建选择素嵌合小鼠，将阐明血小板或内皮选择素在炎症反应中的具体贡献。了解胎儿无疤伤口愈合的机制将为调节产后伤口愈合反应提供替代途径。这不仅对真皮伤口愈合并发症（烧伤挛缩、疤痕疙瘩、肥厚性疤痕、不愈合溃疡等）的治疗产生影响，而且对纤维化是不良后果的所有情况产生影响，例如肺纤维化、狭窄、腹膜粘连、肝纤维化等。此外，了解选择素如何调节胎儿的炎症反应将揭示有价值的信息 这或许可以解释新生儿和早产儿感染的倾向。这些可能会在这些儿童最脆弱的时候提供帮助他们缓解炎症反应的机会。