足细胞EMT是糖尿病肾病（DKD）进展的关键环节，近年来发现FCγRII参与足细胞的EMT，而基质交感分子（STIM）是近年确认的调控EMT的关键靶点。因此，研究STIM和FCγRII的功能与相互作用机制将为治疗DKD提供有力帮助。课题组前期研究发现，FCγRIIa功能的缺失可以预防DKD肾小球损伤，抑制FCγRIIa可减轻足细胞EMT，但STIM如何调控足细胞FCγRII，影响DKD足细胞EMT的作用机制知之甚少。本项目拟在前期工作基础上，通过对DKD患者、DKD大鼠进行转录组测序分析，明确FCγRII和STIM变化规律及参与的信号途径，并利用siRNA干扰沉默STIM上游蛋白，阐明STIM对足细胞FCγRII的调控机制及对足细胞EMT的影响。本研究有助于揭示STIM与FCγRII的关系，为DKD足细胞EMT机制的阐明提供实验依据及干预靶点。

Mesenchymal differentiation（EMT） in the podocytes is the key step of the development of diabetic kidney disease(DKD).Previous studies have demonstrated that podocyte FCγRII activity plays an important role in the evolution of EMT of podocyte. STIM is the crucial target in regulating podocyte EMT. So study the function and interaction mechanism of STIM and FC gamma RII will provide powerful help for the treatment of DKD. In our previous study, we showed that the loss of FCγRIIa function can prevent glomerular injury in DKD, and inhibition of FCγRIIa can reduce the EMT of the podocyte. However, the relationship between STIM and the FCγRII activity of podocytes and their role in the evolution of EMT of podocytes in DKD remain unclear. This project is intended to work on the basis of previous work. Through the analysis of the DKD patients, DKD rat and podocyte cell model with transcription group sequencing, to understand the FCγRII, STIM change law and participate in the signal pathway. Then silencing STIM upstream siRNA interference, respectively. To elucidate the regulation mechanism of STIM on the activity of FCγRII in the podocyte cells and the effect on the EMT of the podocyte cell. This study is helpful to reveal the relationship between the activity of STIM and FCγRII, and to provide experimental basis and intervention targets for elucidating the mechanism of EMT in podocyte cells of DKD.

足细胞EMT是糖尿病肾病（DKD）进展的关键环节，近年来发现FCγRII参与足细胞的EMT，而基质交感分子（STIM）是近年确认的调控EMT的关键靶点，因此，研究STIM和FCγRII的功能与相互作用机制将为治疗DKD提供有力帮助。课题组前期研究发现，FCγRIIa功能的缺失可以预防DKD肾小球损伤，抑制FCγRIIa可减轻足细胞EMT，但STIM如何调控足细胞FCγRII活性，影响DKD足细胞EMT的作用机制知之甚少。本项目拟在前期工作基础上，通过对DKD患者、DKD大鼠及足细胞模型进行转录组测序分析，明确FCγRII和STIM变化规律及参与的信号途径，并利用STIM抑制剂及siRNA干扰分别沉默STIM上游和下游蛋白，阐明STIM对足细胞FCγRII活性的调控机制及对足细胞EMT的影响。本研究有助于揭示STIM与FCγRII的关系，为DKD足细胞EMT机制的阐明提供实验依据及干预靶点。结果表明，与对照组相比，糖尿病肾病患者 STIM1 和STIM2 显著增加，FcγRIIa水平升高，但是FcγRIIb水平下降，这些结果表明FcγRII是STIM的作用靶点，STIM可以调控FcγRII活性水平。进一步动物实验和细胞实验证实高糖能诱导足细胞STIM1、STIM2、CTGF、α-SMA、FcγRIIa表达上调， FcγRIIb表达下调；分子水平抑制STIM1/STIM2可抑制EMT发生，CTGF、a-SMA、FcγRIIa表达下调和FcγRIIb表达上调。DKD诱导的足细胞EMT与足细胞 STIM 过表达相关，这为DKD足细胞EMT的治疗提供了新的治疗途径。