间充质干细胞（MSCs）靶器官归巢率低是目前糖尿病肾病（DN）细胞治疗受限的重要原因，但机制不清。前期发现DN相关miRNAs 中（No.30800534）， 沉默miR-150促进MSCs肾脏归巢。近期RNA-seq等发现DN相关lncRNA Gm2115在DN MSCs增高，通过靶向miR-150和结合Ago2形成lncGm2115-miR-150功能性效应体，使转移因子Cxcr4表达增高。因此，我们推测“lncGm2115-miR-150效应体活化Cxcr4/PI3K/Akt信号途径”是影响DN MSCs归巢的重要原因。本课题以lncGm2115-miR-150效应体为切入点，原代DN MSCs和db/db小鼠为研究对象，研究Gm2115-miR-150具体模式；探讨其对DN MSCs归巢和病情影响；及对下游通路的调控。通过上述研究将有助于阐明MSCs归巢机制，为DN诊治提供突破点。

Low homing ability of mesenchymal stem cells (MSCs) is challenging the celluar therapy of diabetic nephropathy (DN). However, the mechanism is not fully clear. Our previous studies revealed that miRNA participated in DN (NO.30800534), and miR-150 knockdown could promote MSCs homing in DN. Moreover, our recent study showed the DN related lncRNA-lncGm2115 was over-expressed in MSCs of DN, and effector Gm2115-miR-150 which formed by Gm2115 binding to miR-150 and Ago2 could increase the expression of the migration gene-Cxcr4. These suggested that effector lncGm2115-miR-150 may regulate MSCs homing by Cxcr4 related pathway in DN. We will focus on Gm2115-miR-150 in primary stem cells and db/db mice. Firstly, we will study the specific role of effector lncGm2115-miR-150 in DN. Secondly, we will investigate the effects of lncGm2115-miR-150 on cell migration of MSCs and the conditions of the DN mice. Finally, we will examine the role of Gm2115-miR-150 on Cxcr4/PI3K/Akt pathway in DN. Collectively this project may help to elucidate the physiopathological mechanism of DN, and provide a new insight into the prevention and treatment of DN.