IL-28A抑制肺泡上皮细胞的非典型增生向恶性转化的作用机制研究

项目名称： IL-28A抑制肺泡上皮细胞的非典型增生向恶性转化的作用机制研究

项目编号： No.81500078

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 杨达伟

作者单位： 复旦大学

项目金额： 18万元

中文摘要： IL-28A隶属IFN-λ家族，为III型干扰素的一员，为IL-28R的配体，分布具有肿瘤特异性。迄今对IL-28A与肺结节的关系知之甚少。我们的预实验结果提示IL-28A在抑制肺泡上皮细胞从非典型增生向恶性转化中起重要作用。但其作用机制不详。因此我们提出假说：IL-28A/IL-28R能通过激活下游的STAT1信号转导通路来抑制肺结节的恶性转化。为了验证这一假说，我们将采用小鼠原位肺结节模型、人肺癌细胞系SPC和小鼠肺癌细胞系Lewis，利用real time PCR、Western blot、腺病毒载体转染、RNA干扰等手段，从分子、细胞、组织以及动物整体水平等方面：(1)探讨IL-28A在肺泡上皮细胞转化中的作用，(2)明确IL-28A激活下游的STAT1信号转导通路的机制。本研究将从IL-28A这个新视点来揭示肺泡上皮细胞的非典型增生向恶性转化的作用机制，为临床肺结节的防治奠基基础

中文关键词： 非典型增生；肺结节；干扰素；生物标志物

英文摘要： IL-28A belongs to the IFN-λ family, as a member of type III interferon. It acts as a ligand of the IL-28R, which is highly expressed in malignant tumor. However, our knowledge regarding the relationship between IL-28A and lung nodules remains limited. Our preliminary studies indicated that IL-28A plays an important role in the transformation of atypical hyperplasia of alveolar epithelial to malignancy. Thus we hypotheses that IL-28A/IL-28R may activate the STAT1 signal pathway to inhibit transformation of pulmonary nodules into malignancy. To test this hypothesis, mouse orthotropic lung nodules model, human lung cancer cell line (SPC) and mouse lung cancer cell line (Lewis), real time PCR, Western blot, adenovirus mediated over-expression, RNA interference and others will be used to (1) explore the role of IL-28A in the alveolar epithelial transformation, (2) identify whether IL-28A acts through activation of STAT1 signaling pathway at molecular, cellular, tissue and animal levels. Successful completion of this study not only provides an insight into the mechanism of IL-28A in the alveolar epithelial transformation, but also leads to a better clinical treatment of pulmonary nodules.

英文关键词： atypical hyperplasia ;lung nodule;Interferon;biomarker