Collectively, our studies for the first time demonstrate that PGRN protects against podocyte injury in DN, at least in part through maintaining mitochondrial homeostasis via PGRN- Sirt1-PGC-1α/FoxO1 signaling-mediated mitochondrial biogenesis and mitophagy (Fig. 8j), suggesting that PGRN may be an innovative therapeutic strategy for treating patients with DN. This evidence concerns the gene SIRT1 and liver dysplastic nodule.