放射性皮肤损伤是肿瘤放疗中最常见的并发症，严重情况下导致治疗中断，造成肿瘤控制率和治愈率降低。趋化因子CCL27介导的皮肤免疫炎症反应对调节放射性皮肤损伤具有重要作用。分泌CCL27的皮肤角质细胞能够特异性表达连接蛋白Connexin26（Cx26），而研究发现Cx26参与了辐射诱导损伤信号的产生和传导，并且Cx26能与调节CCL27分泌的MAPK和NF-κB/COX-2信号通路相互作用，提示Cx26可能调节辐射后CCL27的分泌。申请人将在体外细胞实验中，研究Cx26表达水平对辐照后CCL27分泌的影响；同时研究Cx26与CCL27表达通路蛋白相互作用，探索Cx26调控CCL27的机理。在动物模型中开展研究，建立Cx26表达与放射性皮肤损伤的关系。研究结果将有利于揭示放射性皮肤损伤的分子机理，为放射性皮肤损伤的防护和治疗提供理论依据。

The radiation-induced skin damage is the most common complication in the patients with cancer radiotherapy. Severe radiation-induced skin damage may attenuate the efficiency of radiotherapy because of limited radiation dose. CC chemokine ligand 27 (CCL27) mediated skin immuno-inflammatory response plays important role in regulation radiation induced skin damage. The keratinocytes of epiderm, from which CCL27 is secreted, could specially express connexin26 (Cx26) that can form gap junction which play important role in mediating radiation damage effects. Previous studies find that Cx26 participate the production and transmission of radiation induced damage signals. And Cx26 also interact with MAPK pathways and NF-κB/COX-2 pathways, which take part in regulating the production and secretion of CCL27. These results indicate that Cx26 might regulate the radiation induced secretion of CCL27. In this study, we will investigate the effects of expression level of Cx26 on secretion of CCL27 after radiation in vitro. Meanwhile, we will try to find the interaction of Cx26 and key proteins that participate in the expression of CCL27, and undercover the mechanisms of the role of Cx26 in regulating CCL27. We will also study the relationship of Cx26 and radiation induced skin damage in mouse models to confirm the findings from in vitro studies. We hope that our results will help to understand the molecular mechanisms of radiation induced skin damage, and provide theory evidences for protection and therapy of radiation induced skin damage during radiotherapy.