miR-23b通过靶定TAB2/3抑制糖尿病肾病纤维化

MicroRNAs(miRNAs)通过与靶基因的相互作用发挥其生物学功能. miR-23b作为抑癌基因，参与了许多肿瘤和自身免疫疾病的发生过程，但其在糖尿病肾病中的作用尚不清楚.为了探讨miR-23b与靶基因TAB2/3作用对糖尿病肾病纤维化的影响，本实验通过建立糖尿病小鼠模型和糖尿病HK-2细胞模型，利用实时定量荧光PCR方法，检测糖尿病小鼠模型肾mRNA表达，发现miR-23b在糖尿病组（Dia组）表达低于正常组（P<0.001）.利用Western印迹检测相关蛋白，结果显示,与正常组相比，TAB2/3，FN和α-SMA在糖尿病组高表达，并且TAB2/3在糖尿病组中持续高表达.利用基因转染技术过表达miR-23b可以同时在mRNA和蛋白水平上抑制TAB2/3，P38和ERK1/2的表达，FN表达也显著降低.以上结果显示：miR-23b可能通过作用靶基因TAB2/3及其信号通路下游，抑制糖尿病肾病纤维化.

MiR-23b Suppresses Diabetic Nephropathy Fibrosis through Targeting TAB2/3

MicroRNAs (miRNAs) function by combining with their target genes. As tumor suppressor genes, miRNAs participate in many disease processes, including tumor formation and autoimmune response. However, their roles in diabetic nephropathy remained unclear. In order to find out the relation between TAB2/3 and miR-23b and how they regulate the diabetic nephropathy fibrosis, we established the diabetic mice models and the HK-2 cells models. Measured by real-time PCR, we learned that the expression of miR-23b in Dia group was down-regulated compared to Con group (P<0.001). The results of Western blotting indicated that the expressions of TAB2/3, FN and α-SMA were up-regulated in Dia group. Meanwhile, TAB2/3 presented a continuous high expression in Dia group. By over-expressing miR-23b through gene transfection, the expressions of TAB2/3, P38 and ERK1/2 at mRNA and protein levels were reduced; the expression of FN was significantly reduced, too. The data suggested that miR-23b inhibit diabetic nephropathy fibrosis by regulating target genes TAB2/3 and downstream of P38 signaling pathways.