Selectins and Fetal wound Healing

选择素和胎儿伤口愈合

• 批准号: 6847819
• 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/6847819
• 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）： 该项目的总体目的是深入了解Selectins在成人和胎儿受伤后调节炎症反应中的作用。胎儿皮肤伤口愈合的特征是炎症反应不足和最小的纤维化。尽管通常认为胎儿炎症细胞不成熟，但通过应用多种刺激，可以在胎儿伤口部位唤起急性炎症反应（带有纤维化）。 Selectins是在白细胞和内皮细胞上表达的细胞表面凝集素分子，它们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，从而对炎症过程产生了显着贡献。这些粘附分子对闭合，修复和疤痕形成的贡献知之甚少。因此，提出了这项研究来评估Selectins在伤口愈合中的作用。该应用将集中在以下假设上：胎儿皮肤伤口中指出的最小炎症是胎儿血小板和内皮细胞上P和E-选择蛋白表达的改变的结果。为了检验该假设，将确定选择素在成年和胎儿血小板和内皮细胞上的相对表达。将研究具有单个单个或选择蛋白组合的靶向缺失的小鼠，以确定选择素缺失对伤口愈合的后果。使用鼠合成胎儿皮肤移植模型并为选择蛋白创建小鼠嵌合，将阐明血小板或内皮选择素在炎症反应中的特定贡献。了解无疤痕胎儿伤口愈合的机制将提供替代途径，以调节产后伤口愈合反应。这不仅对皮肤伤口愈合的并发症的治疗（BUM染色，乳突，肥厚性疤痕，非愈合性溃疡等）有影响这可能解释了新生儿和早产婴儿感染的倾向。然后，当这些孩子最脆弱时，这些可能会提供帮助这些孩子的炎症反应。