基质细胞衍生因子-1在紫外线诱导的皮肤炎症反应中的作用机制研究

Stromal cell-derived factor-1(SDF-1), also known as CXCL12, are widely expressed in various organs of the body. At present, the research on SDF-1 has gradually become a hot spot, especially in the fields of cancer and autoimmune diseases. Studying the mechanism of SDF-1 in the skin inflammation induced by UV may have very important scientific and clinical values. Based on the previous work, we put forward the following hypothesis: 1, Under the ultraviolet light, SDF-1 releases and regulates the skin inflammation through apoptosis and / or autophagy. 2, In the process of regulating the UV induced skin inflammation, PI3K/AKT/mTOR, MEK/ERK, NF-κB, SDF-1, AMPK, Notch and other cell signaling pathways may play a key role. 3, SDF-1 can be used as a potential target for the prevention and treatment of UV induced skin inflammation. We intend to explore the mechanism of SDF-1 in skin inflammation induced by UV both in vitro and in vivo. This new knowledge will provide insight into SDF-1-related genetic pathways and may yield novel perspectives for the prevention and treatment of photo damages.

基质细胞衍生因子-1 (SDF-1)又称趋化因子CXCL12，广泛表达于机体各个器官中。目前对SDF-1的研究逐渐成为热点，特别是在肿瘤和自身免疫性疾病领域。研究 SDF-1在紫外线诱导的皮肤炎症反应中的作用机制，具有非常重要的科研价值和临床应用价值。根据前期的工作基础，我们提出了以下假说：1、在紫外线照射下，SDF-1释放并通过细胞凋亡和/或细胞自噬，调节紫外线诱导的皮肤炎症反应。2、在SDF-1调节紫外线诱导的皮肤炎症反应的过程中，PI3K/AKT/mTOR，MEK/ERK，NF-κB，AMPK，Notch等细胞信号通路的活化起到了关键的作用。3、SDF-1能够作为一个潜在的靶点，预防或治疗紫外线诱导的皮肤炎症反应。我们拟从细胞水平以及动物水平，系统性的研究SDF-1在紫外线诱导的皮肤炎症反应中的作用机制，为皮肤光损伤的防治寻找有效的靶目标，并提供理论依据。

UV辐射与皮肤炎症、皮肤肿瘤密切相关，其可诱导角质形成细胞、皮肤肿瘤细胞（如皮肤鳞状细胞癌（CSCC）细胞）中基质细胞衍生因子1(SDF1)的释放和表达上调。而SDF-1是肿瘤细胞迁移的关键调节因子。Celecoxib是一种非甾体类抗炎药，主要与预防多种癌症有关。然而，塞来昔布和CSCC细胞迁移之间的关系尚未确定。本研究中，我们发现SDF1可通过CXCR4内吞作用诱导CSCC细胞迁移，而塞来昔布通过抑制SDF1诱导的CXCR4内吞作用来抑制CSCC细胞迁移。此外，发现ERK/AKT信号传导途径在该生物学过程中起关键作用。我们的研究提供了有希望的证据表明塞来昔布可以作为CSCC细胞转移的潜在预防药物。