In this study, we found that Cre+/Sirt6fl/fl diabetic mice exhibited a marked increase in the level of uPAR as compared with the Cre+/Sirt6+/+ diabetic mice, indicating that Sirt6 may be one of the critical components that links uPAR to podocyte injury in the pathogenesis of DN. This evidence concerns the gene PLAUR and liver dysplastic nodule.