肾脏纤维化是糖尿病肾病（DN）的主要病理变化，而多因素所致的氧化应激炎性反应是糖尿病肾脏纤维化发病的中心环节。具有明显调节氧化应激炎性反应、且在肾脏高表达的Cx32是否参与调控了糖尿病肾脏纤维化的病理进程？有待阐明。预实验结果显示：糖尿病小鼠肾组织与高糖模型细胞中Cx32表达下调，过表达Cx32明显抑制模型GMCs中FN等炎性纤维化成分的表达、调节肾小管上皮细胞EMT标志物的变化、明显抑制模型细胞中Nox4的表达及活性氧的生成。本项目在此基础上，拟通过体外、体内实验，系统观察Cx32影响模型细胞与模型动物肾组织中FN等炎性纤维化成分及肾小管EMT标志物的变化，确证Cx32调控糖尿病肾脏纤维化的作用；从Cx32影响Nox4、Sirt1-Nrf2通路，研究Cx32调控糖尿病肾脏纤维化的分子机制。本项目对基于氧化应激炎性反应探索抑制糖尿病肾脏纤维化、抗DN新的潜在作用靶点具有重要的研究意义。

Well-described characteristic of diabetic nephropathy (DN) is renal fibrosis. Multifactorial increase of renal oxidative stress and inflammation is the key link in the pathogenesis of diabetic renal fibrosis. Connexin32 (Cx32), which is highly expressed in the kidney, effectively inhibits the oxidative stress and inflammation in mice. It remains to be clarified whether Cx32 participates in the pathological process of diabetic renal fibrosis. Our preliminary results suggested that Cx32 expression was down-regulated in the kidney of diabetic mice and high glucose-induced cells. In addition, overexpression of Cx32 significantly inhibited the expression of FN and other inflammatory and fibrotic components in GMCs as well as high glucose-induced epithelial to mesenchymal transition (EMT) in NRK-52E. Furthermore, Cx32 overexpression suppressed Nox4 expression and the production of ROS in high glucose-induced GMCs and NRK-52E. On the basis of the preliminary results, we aim to observe the effects of Cx32 on FN and other inflammatory and fibrotic components and EMT in high glucose-induced cells and diabetic kidney, and to clarify the role of Cx32 in diabetic renal fibrosis through in vitro and in vivo experiments. Moreover, we wonder whether the mechanism is related to regulating Nox4 expression and Sirt1-Nrf2 pathways. This project is of great significance for exploring the potential targets of inhibiting diabetic renal fibrosis and resisting diabetic nephropathy based on oxidative stress and inflammation.