Keratinocyte Migration and Wound Healing

角质形成细胞迁移和伤口愈合

• 批准号: 8731055
• 负责人: JONATHAN C. JONES
• 金额: $ 33.3万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8731055
• 关键词: 3' Untranslated Regions; Actinin; Actins; Adhesions; Basement membrane; Binding; Biological Assay; Biology; Cell Communication; Cell surface; Cells; Chronic; Collagen Type XVII; Complex; Cytoskeleton; Data; Deposition; Development; Devices; Epidermis; Extracellular Matrix; Family; Family member; Goals; Grant; Hemidesmosomes; Immigration; In Vitro; Integrins; Laminin; Ligands; Link; Mediating; Messenger RNA; Molecular; Monomeric GTP-Binding Proteins; Movement; Mus; Phenotype; Phosphoric Monoester Hydrolases; Play; Process; Proteins; Publications; Relative (related person); Role; Series; Signal Transduction; Skin; Surface; Testing; Traction; Translating; Translations; Wound Healing; cell motility; cofilin; in vivo; insight; keratinocyte; member; migration; monolayer; novel; novel therapeutics; protein function; treatment strategy; wound

DESCRIPTION (provided by applicant): In normal skin integrin 1624 resides at the hemidesmosome and stabilizes cell interaction with laminin-332 in the extracellular matrix. However, there is also evidence that 1624 integrin is involved in cell migration during wound healing. In this renewal, we propose four aims, focused on providing new insight into the molecular mechanisms via which 1624 integrin and its associated proteins regulate keratinocyte motility and wound healing. In aim 1, we present preliminary data suggesting that the 3'UTR of 16 integrin mRNA is an important modulator of the expression of 24 integrin protein. We will test the hypothesis that it encodes a "zipcode" and facilitates the co-localization and co- translation of 16 and 24 integrin mRNA. Aim 2 is premised on preliminary data indicating that the Bullous Pemphigoid Antigen 2 (BPAG2) regulates keratinocyte migration/wound healing by mediating BPAG1e interaction with 1624 integrin. Thus, in aim 3, we will define precisely the molecular mechanisms underlying this function. We will also assess whether BPAG2 is involved in linking 1624 integrin to the actin cytoskeleton and, hence, the motility machinery of the keratinocyte. During the last grant period, we presented evidence that the Bullous Pemphigoid Antigen 1e (BPAG1e, BP230) is required for 1624 integrin-induced signal transduction by mediating 1624 integrin interaction with Rac and Rac activation, an essential requirement for directed skin cell migration in wound healing. We build on this finding in aim 3 by determining precisely how BPAG1e modulates 1624 integrin signaling and function in vitro and in vivo. The results from our three aims should provide mechanistic insight into how 1624 integrin heterodimers and their associated proteins contribute to skin cell motility and the wound healing process.

描述（由申请人提供）：在正常皮肤中，整合素1624驻留在半桥粒处并稳定细胞与细胞外基质中的层粘连蛋白-332的相互作用。然而，也有证据表明1624整合素参与伤口愈合过程中的细胞迁移。在这次更新中，我们提出了四个目标，重点是提供对 1624 整合素及其相关蛋白调节角质形成细胞运动和伤口愈合的分子机制的新见解。在目标 1 中，我们提供了初步数据，表明 16 整合素 mRNA 的 3'UTR 是 24 整合素蛋白表达的重要调节剂。我们将测试以下假设：它编码“邮政编码”并促进 16 和 24 整合素 mRNA 的共定位和共翻译。目标 2 的前提是初步数据表明大疱性类天疱疮抗原 2 (BPAG2) 通过介导 BPAG1e 与 1624 整合素的相互作用来调节角质形成细胞迁移/伤口愈合。因此，在目标 3 中，我们将精确定义该功能背后的分子机制。我们还将评估 BPAG2 是否参与连接 1624 整合素与肌动蛋白细胞骨架，从而影响角质形成细胞的运动机制。第1624章 第1624章康复。我们在目标 3 中的这一发现的基础上，通过精确确定 BPAG1e 如何在体外和体内调节 1624 整合素信号传导和功能。我们三个目标的结果应该提供关于 1624 整合素异二聚体及其相关蛋白如何促进皮肤细胞运动和伤口愈合过程的机制见解。