Melatonin ameliorates hyperglycaemia-induced renal inflammation by inhibiting the activation of TLR4 and TGF-β1/Smad3 signalling pathway.

Melatonin (MT), a hormone secreted from the pineal gland, has beneficial effects on the development of diabetic nephropathy (DN). In our study, we aimed to determine the effects of melatonin on renal inflammation and fibrosis in diabetic nephropathy. In vivo, we evaluated the blood and urine indices of metabolic and renal function, renal inflammation and renal fibrosis in db/db mice after melatonin treatment. Melatonin treatment significantly decreased urinary albumin excretion and reduced the morphological changes in kidney. Additionally, Melatonin reduced the levels of inflammatory factors in kidney such as interleukin-1β, monocyte chemotactic protein-1 and active nuclear factor-κB though toll-like receptor 4 signaling pathway (TLR4). Melatonin also reduced collagen type IV, fibronectin, transforming growth factor-β1 (TGF-β1) and decreased the phosphorylation of Smad3 in the renal tissue. These results indicated that melatonin reduced the inflammation and fibrosis in diabetic nephropathy though TLR4 and TGF-β1/Smad3 signaling pathway. In vitro, melatonin treatment reduced the cell proliferation, inflammatory factors releasing, TLR4 and TGF-β1/Smad3 signaling pathway. Our findings indicated that melatonin may provide a new perspective intervention to halt the hyperglycemia-induced inflammatory response of DN.