肾小球系膜增生是糖尿病肾病(DN)的重要原因，但确切机制尚不清楚。我们发现miRNA参与DN发生（NO.30800534），miR-451抑制DN系膜增生，近期实验发现DN时miR-451与lncRNA 1500026H17RIK存在双负反馈，且系膜细胞沉默1500026H17RIK可加强miR-451的细胞增殖抑制作用，同时使1500026H17RIK 毗邻的DN相关基因IGF-1表达下降，提示miR-451-1500026H17RIK可能通过IGF-1相关途径参与DN系膜增生。本项目以miR-451-1500026H17RIK双负反馈为切入点，以系膜细胞和db/db小鼠为研究对象，研究miR-451与1500026H17双负反馈；探讨此互作对系膜增生的影响；探究DN中此双负反馈对IGF-1/MAPK信号途径异常的调控。通过上述研究将有助于阐明DN系膜增生机制，为DN诊治提供新的突破点。

Glomerular mesangial cell proliferation and extracellular matrix accumulation play important roles in diabetic nephropathy (DN). However, the mechanism is not fully clear. Our studies revealed that miRNA participated in DN (NO.30800534). Our recent study showed the there was a interaction between miR-451 and lncRNA 1500026H17RIK-double feed-back. Moreover, the inhibition of cell proliferation of miR-451 was reinforced by silence of 1500026H17RIK. Also, the DN related gene-IGF-1 which located near 1500026H17RIK was decreased in the si-1500026H17RIK mesangial cells.These suggested that miR-451-1500026H17RIK may regulate the mesangial cell proliferation by IGF-1 related pathway in DN. We will foused on the interaction between the double feed-back of miR-451 and 1500026H17RIK in mesangial cells and db/db mouse. Firstly, we will study the specific relationship of double feed-back between miR-451 and 1500026H17RIK in DN. Secondly, we will investigate the effects of the interaction between miR-451 and 1500026H17RIK on mesangial cell proliferation, extracellular matrix accumulation and the conditions of the DN mice. Finally, we will examine the role of the double feed-back of miR-451 and 1500026H17RIK on IGF-1/MAPK signal 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.