11-LB: Deficiency of Dock 5 Associated with the Progression of Diabetic Glomerular Pathology

DKD is leading cause of ESRD, and recent studies have reported that impaired lipid metabolism in podocytes are essential contributors to the glomerular pathology and DKD. Dock5 belongs to the Dock superfamily, and has been found to associated with obesity and hepatic insulin resistance. Thus, we assessed the role of Dock5 in podocytes and DKD. By using the RNA-Seq data from Nephroseq, we found that Dock5 expression in glomeruli from DKD patients was significantly decreased, and in the signal-cell RNA seq data, Dock5 showed a podocyte exclusive expression pattern. Further, we generated a Dock5 knockout mouse model and induced DKD by STZ/HFD. Dock5 KO led to an increased UACR, kidney/body weight ratio, more severe glomerular sclerosis and reduced podocyte number. The TEM analysis revealed thickening of the GBM and foot-process effacement. In the mechanism exploration, gene-controlled lipogenesis and fatty acid oxidation were significantly changed in podocytes isolated from KO mice. Therefore, Dock5 might be a therapeutic target for DKD and worth to be further explored. Further studies, such as podocyte-specific Dock5 Knockout were needed to confirm the role of Dock5 in DKD. Disclosure H. Qu: None. X. Liu: None. Y. Zheng: None. H. Zheng: None.