UVB启动人角质形成细胞NF-κB信号通路的microRNA调控机制

It’s demonstrated that mid-wave ultraviolet (UVB) activate NF-κB signal pathway, which is an important pathogenesis of photosensitive dermatoses. Recent researches reveal changes of many micro RNAs expressions in UVB-irradiated cells. Mutual regulations, between micro RNAs and target genes, are involved in diverse processions such as cell differentiation or developments of many diseases. So in this study, micro-RNAs expressions in UVB-irradiated keratinocytes would be analyzed by micro-RNA array firstly. Then, the regulating mechanisms of some special micro-RNAs on IκB or IKK, key genes in NF-κB signal pathway, would be explored by antisense oligonucleotide, gene transfection and RNA interference. Based on these results, micro RNAs spectrum and their functions in NF-κB signal pathway would be further investigated in UVB-irradiated keratinocytes. The above-mentioned achievements might play an important role in deeply revealing inflammatory signal pathways in local photosensitive dermatoses as well as provide new directions or targets for the intervention and treatment of photosensitive dermatoses.

已有研究表明，中波紫外线（UVB）引起细胞核因子κB（NF-κB）信号通路的激活是光敏性皮肤病的重要发病机制，近年陆续发现UVB可引起细胞多种微RNAs（micro RNAs）的表达改变。micro RNAs与靶基因间存在着广泛的相互调控，并与细胞分化和疾病发生密切相关。基于此，本课题拟采用micro RNA芯片技术研究UVB辐照人角质形成细胞的micro RNA表达改变，用反义寡核苷酸、基因转导、RNA干扰等技术分析各相关micro RNA对NF-κB信号通路中IκB或IKK基因的调控。通过上述研究，旨在完善UVB辐照角质形成细胞的micro RNAs表达谱，初步探讨UVB启动人角质形成细胞NF-κB信号通路的microRNA调控机制，这对于深入揭示光敏性皮肤病局部的炎症信号通路调控，以及未来开展探索靶向性的干预措施或疾病治疗方法的研究具有重要意义。

已有研究表明，中波紫外线（UVB）引起细胞核因子κB（NF-κB）信号通路的激活是光敏性皮肤病的重要发病机制，近年陆续发现UVB可引起细胞多种微RNAs（micro RNAs）的表达改变。micro RNAs与靶基因间存在着广泛的相互调控，并与细胞分化和疾病发生密切相关。基于此，本课题通过建立UVB辐照人角质形成细胞致光损伤模型，研究不同UVB剂量、不同时相的角质形成细胞NF-B的RNA水平和蛋白质水平的表达变化，发现UVB可通过激活NF-B引起KC的炎症损伤并影响细胞活性改变，而随着UVB能量的增加，细胞活性进一步降低，NF-B活性也有所降低；通过采用micro RNA芯片技术，研究不同UVB剂量、不同时相的角质形成细胞micro RNA的表达变化，建立micro RNA表达谱，并利用生物信息学方法对micro RNA表达谱进行数据分析及靶基因预测，筛选与细胞炎性损伤相关的micro RNAs，研究发现不同剂量UVB处理HaCaT细胞后均出现差异miRNA表达，其中400 mJ/cm2 UVB处理后的HaCaT细胞差异表达的miRNA最为明显，提示了UVB诱导的角质形成细胞差异miRNA的靶基因直接或间接参与了机体的体液免疫和细胞免疫过程，并最终调控光损伤致炎或致瘤的病理过程。