FGF7通过动员内源性干细胞促进肾脏损伤修复的机制

项目名称： FGF7通过动员内源性干细胞促进肾脏损伤修复的机制

项目编号： No.81500519

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： 谭晓华

作者单位： 青岛大学

项目金额： 18万元

中文摘要： 急性肾损伤（acute kidney injury, AKI）是临床常见的危急重症。缺血再灌注损伤(I/RI)造成肾小管上皮细胞大量坏死和凋亡是AKI发生的主要原因之一，寻找有效的方法来补充丢失的实质细胞，是促进损伤肾脏修复和重建的首要目标。干细胞具有多向分化潜能，目前研究发现内源性干细胞的动员与肾脏等多种器官损伤的修复过程密切相关。本研究的前期工作发现生长因子类药物FGF7能够保护缺血损伤肾脏的组织结构，促进肾脏功能的恢复；此外，给予FGF7能够显著增高外周血中的造血干细胞数量，并促进细胞迁移相关的转录因子及趋化因子的表达。因此，本项目拟在前期工作基础之上，采用小鼠缺血性肾脏损伤模型，首次探讨FGF7调控内源性干细胞动员的分子机制及其在肾脏损伤修复中的作用。旨在为肾脏损伤的治疗和修复研究提供全新的思路和药物靶点，也为FGF7等生长因子类药物的新药开发奠定更为全面和深入的理论基础。

中文关键词： 急性肾损伤；干细胞；缺血再灌注损伤；成纤维细胞生长因子7

英文摘要： Acute kidney injury(AKI) is a severe and relatively common clinical syndrome that carries a considerable mortality. Ischemic reperfusion injury(I/RI) is associated with extensive renal tubular cell damage and represents a major cause for AKI. Therefore, it is of critical importance to discover effective means to restore the lost renal parenchymal cells in order to promote the repair/reconstruction processes following ischemic reperfusion induced renal damage..Stem cells are known to possess the potential of multi-directional differentiation. Indeed, research in the past years have firmly established that the mobilization of endogenous stem cells to the injured sites are highly pertinent to the repair processes in various organ/tissue injuries including the kidney. .Our preliminary results showed that FGF7 could protect the kidney tissue from ischemic renal injury and promote the recovery of renal function as well as structural integrity. In addition, FGF7 administration significantly increased the number of hematopoietic stem cells in the peripheral blood and enhanced the expression of certain transcription factors and chemokines important in the regulation cell migration. .The current project aims to investigate, for the first time, the molecular mechanism of FGF7 in regulating mobilization of endogenous stem cells and its effect on the repair process of ischemic renal injury using a genetically engineered mouse model. The goal of the proposed research is not only to uncover novel drug target for the treatment of ischemic kidney injury, but also to lay a more comprehensive theoretical framework for the development of growth factor-based drugs, such as FGF7, for regenerative medicine and disease therapy.

英文关键词： Acute kidney injury;Stem cells;Ischemia reperfusion injury;Fibroblast growth factor 7