IL-6调控胆管损伤修复相关microRNA的鉴定及功能研究

项目名称： IL-6调控胆管损伤修复相关microRNA的鉴定及功能研究

项目编号： No.81200319

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 蒋桂星

作者单位： 浙江大学

项目金额： 23万元

中文摘要： 胆管损伤后修复不良是目前限制肝胆外科发展的重要因素之一。IL-6具有促胆管上皮细胞（ BEC）增殖和迁移的能力，在胆管损伤修复中起重要作用。研究显示微小RNA（miRNAs）在组织损伤修复中扮演重要角色。本课题拟重点研究IL-6调控的miRNAs在胆管修复中的作用及分子机制。拟利用miRNA芯片、荧光定量PCR等技术，筛选并确定IL-6诱导BEC后差异表达的miRNAs；在BEC中过表达或下调侯选miRNAs，观察其对IL-6介导的BEC增殖、迁移等的影响；采用生物信息学预测并结合报告基因检测的方法，确定miRNA的靶基因；应用基因过表达、小RNA干扰等技术，研究miRNA靶基因在调控BEC生物学行为中的功能；建立急性胆管炎动物模型，研究体内调控miRNA对胆管损伤修复的影响。本研究将加深对IL-6调控BEC生物学行为的分子机制的认识，为胆管损伤后正常修复提供新的干预靶点。

中文关键词： 胆管损伤；白介素-6；微小RNA；信号转导；

英文摘要： Incomplete healing after biliary injury is a big challenge faced by hepatobiliary surgeons. Interleukin-6 (IL-6) is capable of enhancing the proliferation and migration of biliary epithelial cells (BECs) and may thus play a key role in repair of biliary injuries. Accumulating evidence indicates that microRNAs (miRNAs) are involved in tissue regeneration. In this project, we aim to clarify the functions of miRNAs induced by IL-6 in biliary repair and the associated molecular mechanisms. By combining studies in cell culture and animal models, we sought to: (1) screen for and verify the miRNAs stimulated by IL-6 in BECs; (2) elucidate the biological functions of candidate miRNAs in the IL-6-mediated BEC proliferation and migration; (3) identify the target genes of miRNAs and uncover their functions in the regulation of BEC migration and proliferation; (4) and investigate the effects of manipulating the expression of miRNAs on biliary regeneration in a animal model of acute cholangitis. This project will provide more insight into the molecular mechanisms for IL-6-mediated repair of biliary lesions, and may offer a novel promising target for promotion of biliary regeneration.

英文关键词： biliary injury；IL-6；microRNA；signal transduction；