基于仿生肾单位微流控芯片研究miR-30a抑制糖尿病肾病进展的作用和机制

Diabetic nephropathy (DN) is the most common secondary glomerular disease. It is important that construction a suitable in vitro model which is able to reproduce disease progression, looking for key signaling pathways and intervention targets. We have successfully established “glomerulus-on-a-chip” and “renal tubular-on-a-chip” to reproduce disease progression of hypertensive renal damage and albuminuria nephropathy. And we screen out the key risk factors of diseases. Recent literatures and our previous research found that Wnt/β-catenin signaling pathway on podocyte is the core pathways of promoting glomerular sclerosis. Intervention expression of miR-30a, endogenous target genes in podocyte, play a key role in glomerular disease. Wnt/β-catenin pathway might be regulated by miR-30a in podocyte, but the mechanism is still not clear. In this study, we plan to establish a “nephron-on-a-chip” to imitate the pathological changes of DN in vitro. Subsequently we further verify the targeting regulation of miR-30a expression restrain DN progress through inhibating the activation of Wnt/β-catenin pathway. The prospective results may reveal the new research platform and therapeutic target for the studies of DN.

糖尿病肾病（DN）是临床最常见的继发性肾小球疾病。构建适合体外研究平台，使病理进展可视化，寻找关键致病信号通路及干预靶点有重要意义。我们前期构建了“肾小球”及“肾小管”仿生微流控芯片模型，从临床常见的高血压肾损害和蛋白尿性肾病为出发点，成功重现疾病进展过程并筛选出关键致病因素。同时查阅文献和我们前期研究发现，足细胞上Wnt/β-catenin信号通路是促进肾小球硬化的核心通路；干预足细胞中内源性靶基因miR-30a表达对肾小球疾病进展起关键作用，Wnt/β-catenin信号通路极有可能受其调控，然其具体机制不清。本研究在此基础上，以微流控芯片组织工程技术为核心技术构建仿生“肾单位”芯片DN模型，以足细胞上miR-30a为干预靶点，进一步揭析miR-30a-Wnt/β-catenin信号通路在DN进展中的作用，为DN防治提供新研究平台与干预策略。

糖尿病肾病（DN）是临床最常见的继发性肾小球疾病。构建适合体外研究平台，使病理进.展可视化，寻找关键致病信号通路及干预靶点有重要意义。我们前期构建了“肾小球”及“肾.小管”仿生微流控芯片模型，从临床常见的高血压肾损害和蛋白尿性肾病为出发点，成功重现.疾病进展过程并筛选出关键致病因素。同时查阅文献和我们前期研究发现，足细胞上Wnt/β-c.atenin信号通路是促进肾小球硬化的核心通路；干预足细胞中内源性靶基因miR-4449表达对肾.小球疾病,进展起关键作用，Wnt/β-catenin信号通路极有可能受其调控，然其具体机制不清。.本研究在此基础上，以微流控芯片组织工程技术为核心技术构建仿生“肾单位”芯片DN模型，.以足细胞上miR-4449为干预靶点，进一步揭析miR-4449-Wnt/β-catenin信号通路在DN进展中的.作用，为DN防治提供新研究平台与干预策略