IL-24调控维持上皮细胞分化稳态的作用及机制研究

项目名称： IL-24调控维持上皮细胞分化稳态的作用及机制研究

项目编号： No.81470707

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郭传瑸

作者单位： 北京大学

项目金额： 73万元

中文摘要： 人类许多疾病都与上皮细胞的分化和稳态有关，研究调控上皮稳态调控机制对某些疾病的预防和治疗有重要意义。目前,白介素24（IL-24）对调控上皮分化和稳态的影响及其机理尚无报道。本课题根据我们的前期研究结果，初步认定IL-24对调控上皮分化和稳态起重要的作用，并提出了IL-24对上皮细胞分化及维持稳态的钟摆理论，即IL-24可以维持上皮细胞分化稳态，低分化及过分化上皮细胞在IL-24 的作用下，均可以维持在特定的中间状态分化。为此我们在细胞层面、上皮三维培养层面及IL-24转基因及敲除动物上皮标本层面，拟通过IL-24蛋白刺激上皮细胞、建立表达IL-24受体的口腔上皮细胞系，Real time PCR、Western blot、荧光素酶实验、免疫共沉淀、上皮三维培养和IL-24转基因和敲除动物上皮组织标本分析上皮分化程度等技术，来探讨IL-24调控维持上皮分化和稳态中的作用及调控机理。

中文关键词： 白介素24；上皮细胞分化；上皮稳态；分子机制

英文摘要： Many diseases are related with the disorder of epithelial differentiation and homeostasis in human. To date, the effect and mechanism of interleukin 24 (IL-24) on epithelial differentiation and homeostasis are still unreported. In this proposal, based on our preliminary results, we initially deduced that Il-24 could play a very important role in the maintenance of the epithelial differentiation and homeostasis. Meanwhile, we advanced a pendulum swing theory to explain how IL-24 works on regulation of epithelial differentiation and homeostasis. That is, IL-24 can maintain the homeostasis of epithelium. Both low-differentiated and high -differentiated epithelial cells can differentiate into the middle differentiated status of epithelium under IL-24 treatment. We therefore design the experiments at cell level, at three-dimensional epithelial cell cultivation level, and at the IL-24 transgenic and knockout mice level, through cell culture and treatment with IL-24 method to study the effect of IL-24 on the differentiation of epithelial cells HaCat, oral squaumous cells WSU-HN6, and embryo stem cells; establishment IL-24 receptor transfected stable cell line to investigate the model of action of IL-24, using real time PCR, western blot, immunoprecipitation and immunostaining to study the expression of epithelial differentiation markers and the signal transduction involved; using luciferase to explore the regulation of IL24 at DNA level; three-dimensional epithelial cell culture and the skin tissue specimens from IL-24 transgenic and knockout mice to confirm the data obtained. Our final goal is to investigate and understand the effect of IL-24 on epithelial differentiation and how Il-24 works, the underlying mechanism.

英文关键词： Interleukin 24;Epithelail diferentiation;Epithelial homeostasis;Molecular mechanism