Melatonin: a potential therapeutic agent for alleviating renal tubular epithelial cell interstitial transformation.

Melatonin (Mel) has been documented to modulate epithelial-mesenchymal transition (EMT) in cellular systems. The interstitial transformation of renal tubular epithelial cells constitutes a key pathogenic mechanism underlying renal fibrosis. This study aims to elucidate the role of Mel in the EMT process of renal tubular epithelial cells. A rat model of unilateral ureteral obstruction (UUO) was developed through unilateral ureteral ligation, followed by treatment with Mel (5, 10, and 20 mg/kg). Subsequent analyses included histopathological examination, measurement of creatinine and blood urea nitrogen levels, immunofluorescence analysis of fibronectin (FN), and immunohistochemical analysis of alpha-smooth muscle actin (α-SMA). Transforming growth factor-beta 1 (TGF-β1) initiates a fibrotic response in NRK-52E cells, which is subsequently treated with Mel (0. 1, 1, and 10 μmol/L). Evaluates cell viability, migration, and the expression of EMT related proteins, including FN, α-SMA, collagenase I, and E-cadherin. To validate the regulatory interaction between miR-153-3p and Forkhead transcription factor o subfamily member 3A (FOXO3A), cells are transfected with miR-153-3p mimics or siRNA targeting FOXO3A (si-FOXO3A). In results Mel exhibits a dose-dependent capacity to ameliorate renal injury and rectify glomerular structural abnormalities in UUO rat models. In comparison to UUO model rats, melatonin significantly reduced the expression levels of FN and α-SMA. In vitro studies demonstrated that Mel inhibited the activity and migratory behavior of cells, as well as the protein expression levels of FN, α-SMA, and collagenase I in NRK-52E cells. Relative to the control group, UUO rats and TGF-β1-induced NRK-52E cells exhibited elevated expression of miR-153-3p and reduced FOXO3A. In vitro models further revealed that upregulation of miR-153-3p or downregulation of FOXO3A can negate the protective effects of Melatonin on TGF-β1-induced EMT. Concluding, Mel inhibits miR-153-3p, thereby promoting the transcription of FOXO3A in UUO rats, which alleviates renal injury and attenuates TGF-1-induced EMT in cells.