Regulation of Skin Wound Epithelialization by Galectin-3

Galectin-3 调节皮肤伤口上皮化

• 批准号: 7315928
• 负责人: FU-TONG LIU
• 金额: $ 19.61万
• 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 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7315928
• 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)：Galectins是一个动物凝集素家族，由其对半乳糖苷和共同蛋白序列的亲和力定义。Galectin-3是研究最广泛的成员，表达于多种细胞，包括角质形成细胞和巨噬细胞。我们目前的观点是，内源性Galectin-3可以通过细胞内机制调节细胞功能，如细胞迁移、生长和凋亡。同时，当Galectin-3以外源方式加入培养细胞后，可以通过与细胞表面的糖链结合来诱导跨膜信号转导。现有信息和我们的初步研究表明，Galectin-3可能通过对巨噬细胞和角质形成细胞的作用而在伤口愈合过程中发挥重要作用：1.利用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，我们最近还证明了内源性Galectin-3正向调节巨噬细胞的迁移。因此，我们认为内源性Galectin-3可以促进创伤愈合过程中单核/巨噬细胞的迁移。我们还提出，在皮肤创伤部位加入Galectin-3可以吸引单核/巨噬细胞。2.我们发现内源性Galectin-3正向调节角质形成细胞的迁移，并且Galectin-3存在于迁移的角质形成细胞的前沿。我们还证明了Galectin-3在体内和体外小鼠皮肤创伤再上皮化过程中发挥着重要作用。我们的合作者已经证明，内源性Galectin-3对于角膜伤口的再上皮化是必不可少的，而重组Galectin-3促进了角膜伤口的修复。拟议的研究旨在明确确定Galectin-3在皮肤创伤修复的炎症和再上皮化阶段的作用。我们将讨论内源性和外源性添加的重组蛋白Galectin-3的功能。1：研究Galectin-3在皮肤创伤愈合过程中巨噬细胞功能中的作用2：Galectin-3调节角质形成细胞迁移的机制研究3：外源性Galectin-3对伤口再上皮化的影响研究完成后，应能全面了解内源性Galectin-3如何在皮肤伤口愈合的炎症和再上皮化阶段发挥作用。这项研究还应该揭示外源添加的Galectin-3蛋白对皮肤伤口再上皮化的影响。所获得的信息将有助于为研究重组Galectin-3作为治疗皮肤伤口的治疗剂奠定基础。表演现场(S)(组织，城市，州)加州大学戴维斯分校，萨克拉门托医疗中心，加利福尼亚州皮肤伤口无法愈合是一个主要的医疗问题。这项研究项目涉及了解一种名为Galectin-3的蛋白质的功能，即它对参与皮肤伤口愈合的不同细胞群的特性的调节。长期目标是开发改进的皮肤伤口治疗方法。