CD74 and Wound Healing

项目摘要 粘膜上皮屏障在许多情况下都会被破坏，例如外科手术、创伤、 炎症性肠病、缺血和感染。粘膜上皮细胞的再生对粘膜至关重要 伤口闭合和愈合。我们的总体目标是了解导致有效粘膜的机制 伤口闭合。 这一建议建立在我们最近发现的一种新的肠道粘膜伤口修复机制的基础上，该机制涉及 CD74信号。CD74是MIF细胞因子的受体。我们的研究是由三个重要和 创新问题：驱动上皮细胞CD74受体表达的机制是什么(目标1)？我们能不能 安全有效地刺激CD74(目标2)？基因变异的功能后果是什么？ CD74活性(目标3)？ 从这些研究中获得的知识将促进我们对CD74生物学和 粘膜伤口修复，并可能导致新的治疗策略，以促进粘膜伤口愈合。

Project Summary The mucosal epithelial barrier becomes disrupted in many conditions such as surgical procedures, trauma, inflammatory bowel diseases, ischemia, and infections. Epithelial cell regeneration is essential for mucosal wound closure and healing. Our overall goal is to understand the mechanisms that lead to effective mucosal wound closure. This proposal builds on our recent discovery of a novel intestinal mucosal wound repair mechanism involving CD74 signaling. CD74 is the receptor for the MIF cytokine. Our research is motivated by three important and innovative questions: What is the mechanism that drives epithelial CD74 receptor expression (Aim 1)? Can we safely and effectively stimulate CD74 (Aim 2)? What are the functional consequences of genetic variation on CD74 activity (Aim 3)? Knowledge gained from these studies will advance our mechanistic understanding of CD74 biology and mucosal wound repair, and may lead to new therapeutic strategies for promoting mucosal wound healing.