PGE2/EP2介导间充质干细胞向急性肺损伤肺组织归巢的机制研究

项目名称： PGE2/EP2介导间充质干细胞向急性肺损伤肺组织归巢的机制研究

项目编号： No.81201489

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 陆晓旻

作者单位： 东南大学

项目金额： 25万元

中文摘要： 肺实质细胞广泛受损及弥漫性炎症反应是ALI的主要特点，MSC治疗是其重要方向，但MSC向损伤肺组织归巢率低且机制不清，探索MSC归巢的机制及可能的干预手段是MSC修复肺损伤的关键。PGE2是ALI的重要产物，它不仅参与炎症调控，还参与肿瘤细胞迁移，MSC可诱导性表达PGE2受体EP2，PGE2是否参与MSC向肺组织归巢尚不清楚。本研究拟通过基因转染，构建高表达EP2的MSC，通过细胞实验及LPS 诱导ALI模型的动物实验，①观察PGE2对EP2高表达的MSC定向迁移及向肺组织归巢的影响，证实PGE2对MSC的趋化作用；②观察MSC表面粘附分子表达，明确PGE2能否增加MSC表面粘附分子水平进一步促进MSC的归巢；③观察EP2高表达的MSC向损伤肺组织归巢及肺损伤修复情况，阐明PGE2促进EP2高表达的MSC向肺组织归巢而发挥肺保护作用。既明确了MSC的归巢机制又为ALI治疗提供新的途径。

中文关键词： 前列腺素E2；间充质干细胞；肺损伤；归巢；

英文摘要： Acute lung injury(ALI) is a devastating clinical syndrome which characterized by diffuse damage of lung parenchymal cells and excessive inflammatory response, mesenchymal stem cells (MSC) may be useful for the treatment of ALI and can be found within the lung tissues after transplantation. The mechanisms determining MSC recruitment to the lung remain unclear and the rate of engraftment is very low.Prostaglandin E2(PGE2) is highly expressed in the injuried lung tissues and acts as an anti-inflammatory cytokine which is in contrast to pro-inflammatory properties previously considered.Recently,A number of studies have showed that PGE2 plays an important role in the process of cancer metastasis,which increased both cell migration and proliferation. Interestingly, in our previous study, we found that there was expression of E-type prostaglandin receptor 2 (EP2) in MSC,whether PGE2 particpate in the engrafment process of MSC is still unknown. In this study, We investigate the role of PGE2 and its receptor EP2 in the homing process of MSC. MSCs are isolated from 6 week-old C57BL/6 male mice and transduce with the EP2 gene, using a lentivirus vector. In vitro study and in vivo mouse model, the LPS-induced lung injury, we quantify the migration and engraftment of MSC carrying EP2 to the injured lung. In addition, w

英文关键词： prostaglandin E2；mesenchymal stem cells；lung injury；homing；