Regulation of Skin Wound Epithelialization by Galectin-3

Galectin-3 调节皮肤伤口上皮化

• 批准号: 7470573
• 负责人: FU-TONG LIU
• 金额: $ 16.01万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7470573
• 关键词: Address; Affinity; Amino Acid Sequence; Animal Lectins; Apoptosis; Binding; Cell Count; Cell physiology; Cell surface; Cells; Cities; Consensus; Corneal Injury; Cultured Cells; Data; Family; Galactose Binding Lectin; Galactosides; Galectin 3; Goals; Growth; Healed; Inflammation; Inflammatory; Inflammatory Response; Investigation; Medical; Medical center; Membrane Microdomains; Methods; Modeling; Mus; Numbers; Pathologic Processes; Peptide Sequence Determination; Phase; Play; Polysaccharides; Population; Process; Property; Proteins; Recombinant Proteins; Recombinants; Regulation; Reporting; Research Design; Research Project Grants; Research Proposals; Role; Signal Transduction; Signal Transduction Pathway; Site; Skin; Staging; Therapeutic Agents; Time; Topical application; Wound Healing; cell motility; extracellular; healing; improved; in vivo; keratinocyte; macrophage; member; migration; monocyte; performance site; wound

DESCRIPTION (provided by applicant): Galectins are a family of animal lectins defined by their affinity for ¿-galactosides and consensus protein sequences. Galectin-3 is the most extensively studied member and is expressed by a variety of cells, including keratinocytes and macrophages. Our current view is that endogenous galectin-3 can regulate cellular functions, such as cell migration, growth and apoptosis, through intracellular mechanisms. In the mean time, when added exogenously to cultured cells, galectin-3 can induce transmembrane signal transduction by binding to cell surface glycans. Existing information as well as our preliminary studies suggests that galectin-3 may contribute significantly to the wound healing process through its effects on macrophages and keratinocytes: 1. Studies of various inflammation models using gal3-/- mice have provided convincing evidence for the role of galectin-3 in promotion of inflammation. In addition, we have recently demonstrated that endogenous galectin-3 positively regulates migration of macrophages. Thus, we propose that endogenous galectin-3 can promote migration of monocytes/macrophages during wound healing. We also propose galectin-3 added to skin wound sites can attract monocytes/macrophages. 2. We have found that endogenous galectin-3 positively regulates migration of keratinocytes and galectin-3 is present at the leading edges of migrating keratinocytes. We have also demonstrated that galectin-3 plays an important role in skin wound re-epithelialization in mice both ex vivo and in vivo. Our collaborators have shown that endogenous galectin-3 is essential for re-epithelialization of corneal wounds and recombinant galectin-3 promotes corneal wound repair. The proposed studies are designed to definitively establish the role of galectin-3 in the inflammatory and re-epithelialization phases of skin wound repair. We will address the functions of both galectin-3 present endogenously and exogenously added recombinant protein. 1: Investigation of the role of galectin-3 in the function of macrophages during skin wound healing 2: Investigation of the mechanism by which galectin-3 regulates keratinocyte migration 3: Investigation of the effects of exogenous galectin-3 on wound re-epithelialization The completion of the proposed studies should afford a comprehensive picture of how endogenous galectin-3 functions in the inflammatory and re-epithelialization phases of skin wound healing. The studies should also reveal the effects of exogenously added galectin-3 protein to skin wound re-epithelialization. The information obtained will help set the stage for investigation of recombinant galectin-3 as a therapeutic agent for treatment of skin wounds. PERFORMANCE SITE(S) (organization, city, state) UC Davis, Medical Center Sacramento, CA Skin wounds that do not heal are a major medical problem. This research project deals with understanding of the functions of a protein called galectin-3 in terms of its regulation of properties of different cell populations involved in healing of skin wounds. The long-term goal is to develop improved methods for treatment of skin wounds.

描述（由应用提供）：甲状腺素是由动物讲座的家族，其对 - 半乳糖苷和共有蛋白序列的亲和力定义。 Galectin-3是最广泛的研究构件，由包括角质形成细胞和巨噬细胞在内的多种细胞表达。我们目前的观点是，内源性半乳糖素3可以通过细胞内机制调节细胞迁移，生长和凋亡等细胞功能。同时，当清晰地添加到培养的细胞中时，lectectin-3可以通过结合与细胞表面糖质结合来诱导跨膜信号转导。现有信息以及我们的初步研究表明，Galectin-3可能通过其对巨噬细胞和角质形成细胞的影响来对伤口愈合过程产生重大贡献：1。使用GAL3 - / - 小鼠对各种炎症模型的研究为GALECTIN-3在促进炎症中的作用提供了令人信服的证据。此外，我们最近证明，内源性乳糖素3积极调节巨噬细胞的迁移。这也是我们还提出，内源性半乳糖素3可以在伤口愈合过程中促进单核细胞/巨噬细胞的迁移。我们还提出，添加到皮肤伤口部位的内源性半乳糖素3可以吸引单核细胞/巨噬细胞。 2。我们发现，内源性半乳糖素3对角质形成细胞的迁移和半乳糖素3的迁移存在于迁移的角质形成细胞的领先边缘。我们还证明，lectectin-3在离体和体内小鼠的皮肤伤口再上皮上起重要作用。我们的合作者表明，内源性半乳糖素3对于重新上皮的角膜伤口上皮化至关重要，重组乳糖素-3可促进角膜伤口修复。拟议的研究旨在定义Galectin-3在皮肤伤口修复的炎症和再上皮阶段的作用。我们将解决乳糖素3的功能内源和外源添加的重组蛋白。 1：研究六叶乳素3在皮肤伤口愈合过程中巨噬细胞功能的作用的研究2：研究乳肠蛋白3调节角质形成细胞迁移的机制3：研究外源性半乳糖素3对伤口重新上皮重新启动的影响的研究，应对拟议的研究的全面作用 - 炎症和炎症的全面作用 - 孔 - 且对内生的作用 - 对良好的galectir- galectiriation-enipition-3皮肤伤口愈合的阶段。这些研究还应揭示外源添加的乳肠蛋白3蛋白对皮肤伤口再上皮上皮化的影响。获得的信息将有助于为重组Galectin-3作为治疗皮肤伤口的治疗剂的投资奠定基础。性能地点（S）（组织，城市，州）UC Davis，萨克拉曼多医疗中心，加利福尼亚州的皮肤伤口，无法愈合是一个主要的医疗问题。该研究项目涉及对称为Galectin-3的蛋白质功能的理解，该蛋白质对与皮肤伤口愈合有关的不同细胞种群的性质调节。长期目标是开发改进的皮肤伤口治疗方法。