Melatonin suppresses cellular senescence in diabetic kidney disease though the Wnt/β-catenin signaling pathway.

Abstract

Cellular senescence plays a contributory role in the development and progression of diabetic kidney disease (DKD). Melatonin shows potent anti-senescent and anti-inflammatory effects, with demonstrated benefits in DKD. Delineation of the mechanisms through which melatonin delays cellular senescence to ameliorate the progression of DKD will enhance our understanding and ability to treat the disease. Therefore, to elucidate the effects and underlying mechanisms of melatonin, we established streptozotocin (STZ)-induced diabetic mouse models and high glucose (HG)-stimulated human renal cortical proximal tubule epithelial (HK-2) cell models. Cellular senescence was assessed by western blotting, quantitative real-time PCR (qPCR), and β-galactosidase (SA-β-gal) staining. Renal histopathological injury was evaluated by hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining, along with renal function measurements. The results showed that melatonin administration significantly improved renal function and attenuated histopathological damage in diabetic mice. Furthermore, melatonin effectively reduced the levels of cellular senescence marker proteins (p53, p21, p16