白细胞分化抗原36(CD36)属于B型清道夫受体家族，是调控机体免疫和代谢稳态的重要分子。我们和其他课题组的前期工作表明：糖尿病肾病（DN）的患者和动物模型中，肾脏CD36表达升高，且与肾损伤呈正相关；CD36缺失可以改善DN小鼠的肾脏病变和肾功能降低。.自噬-溶酶体通路受损在DN发生发展中起到关键作用。我们前期发现：抑制CD36可以促进转录因子EB (TFEB)的核转位，改善自噬-溶酶体功能。因此，本项目拟在大量前期工作基础上，从人群、动物模型和细胞模型三个层次，全面深入研究CD36在DN病变中的作用，并探讨CD36负性调控TFEB-自噬溶酶体通路参与DN发生发展的分子机制，这将加深人们对DN发病机制的认识，可能为临床上有效防治DN提供新的靶点。

CD36 is a multi-functional class B scavenger receptor, which acts as an important modulator of lipid homeostasis and immune responses. Previously, we and other groups have demonstrated that CD36 expression was significantly increased in kidneys from patients with DN and DN animal models. Furthermore, CD36 deficiency protected mice from kidney injury in a STZ/HFD-induced DN model. Thus, these data supported that CD36 plays a key role in the development and progression of DN..Autophagy is an evolutionary-conserved lysosomal-mediated protein degradation process that cells use to remove protein aggregates and damaged or excess organelles. Impairment of autophagic flux is closely related to the development and progression of glomerulosclerosis, kidney fibrosis and diabetic nephropathy. We have also observed that CD36 deficiency enhanced autophagic flux in kidneys from STZ/HFD-induced DN mice. Transcription factor EB (TFEB) is a master gene for autophagy, which coordinates expression of lysosomal hydrolases, multiple membrane proteins and genes involved in autophagy. We found that while knockdown of CD36 expression promoted TFEB translocation into nucleus of HK2 cells, CD36 overexpression hindered TFEB from translocation into nucleus. Therefore, we hypothesize that CD36 negatively regulates TFEB pathway, inducing autophagic impairement. Following this line, in this project, we plan to verify the importance of CD36 in DN patients and animal models. Moreover, we will investigate whether CD36 causes DN via impairing TFEB-regulated autophagic process and explore the underlying mechanisms.