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（由申请人提供）：半乳糖凝集素是动物凝集素家族，通过其对β-半乳糖苷和共有蛋白序列的亲和力来定义。 Galectin-3 是研究最广泛的成员，由多种细胞表达，包括角质形成细胞和巨噬细胞。我们目前的观点是内源性半乳糖凝集素3可以通过细胞内机制调节细胞功能，例如细胞迁移、生长和凋亡。同时，当外源添加到培养细胞中时，半乳糖凝集素3可以通过与细胞表面聚糖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细胞的影响对伤口愈合过程做出重大贡献： 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半乳糖凝集素3对巨噬细胞的迁移具有正向调节作用。因此，我们提出内源性半乳糖凝集素3可以促进伤口愈合过程中单核细胞/巨噬细胞的迁移。我们还建议将半乳糖凝集素 3 添加到皮肤伤口部位可以吸引单核细胞/巨噬细胞。 2.我们发现内源性半乳糖凝集素3正向调节角质形成细胞的迁移，并且半乳糖凝集素3存在于迁移的角质形成细胞的前缘。我们还证明，galectin-3 在小鼠离体和体内皮肤伤口再上皮化中发挥着重要作用。我们的合作者已经证明，内源性半乳糖凝集素 3 对于角膜伤口的上皮化至关重要，重组半乳糖凝集素 3 可以促进角膜伤口修复。拟议的研究旨在明确确定 galectin-3 在皮肤伤口修复的炎症和上皮再生阶段中的作用。我们将探讨内源性和外源性添加重组蛋白的半乳糖凝集素 3 的功能。 1：研究半乳糖凝集素 3 在皮肤伤口愈合过程中巨噬细胞功能中的作用 2：研究半乳糖凝集素 3 调节角质形成细胞迁移的机制 3：研究外源性半乳糖凝集素 3 对伤口再上皮化的影响 所提出的研究的完成应全面了解内源性半乳糖凝集素 3 在炎症和上皮细胞再形成中的功能 皮肤伤口愈合的阶段。研究还应揭示外源添加半乳糖凝集素 3 蛋白对皮肤伤口上皮再生的影响。获得的信息将有助于为重组半乳糖凝集素 3 作为皮肤伤口治疗剂的研究奠定基础。表演地点（组织、城市、州） 加州大学戴维斯分校，萨克拉门托医疗中心，加利福尼亚州 不愈合的皮肤伤口是一个主要的医疗问题。该研究项目旨在了解一种名为 galectin-3 的蛋白质在调节参与皮肤伤口愈合的不同细胞群特性方面的功能。长期目标是开发治疗皮肤伤口的改进方法。