Molecular mechanisms of melatonin in the reversal of LPS-induced EMT in peritoneal mesothelial cells

• Published in: Molecular medicine reports Vol. 14; no. 5; pp. 4342 - 4348
• Main Authors: Shi, Shuaishuai, Zhang, Yiqiang, Wen, Wenbin, Zhao, Yine, Sun, Lin
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-11-2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Actin; Antioxidants; Antioxidants - administration & dosage; c-Jun protein; Cell culture; Cell Line; Cytokines; Developing countries; E-cadherin; epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - drug effects; Epithelium - drug effects; Fibrosis; Gene expression; Gene Expression Regulation - drug effects; Genetic aspects; Growth; Health aspects; Humans; Immunofluorescence; Inflammation; Inflammation - drug therapy; Inflammation - etiology; Inflammation - metabolism; JNK Mitogen-Activated Protein Kinases - genetics; JNK protein; Kidney Failure, Chronic - chemically induced; Kidney Failure, Chronic - pathology; Kidney Failure, Chronic - therapy; Kidneys; Kinases; LDCs; lipopolysaccharide; Lipopolysaccharides; Lipopolysaccharides - toxicity; Melatonin; Melatonin - administration & dosage; Mesenchyme; Mesothelium; Molecular modelling; Peritoneal dialysis; Peritoneal Fibrosis - drug therapy; Peritoneal Fibrosis - etiology; Peritoneal Fibrosis - genetics; Peritoneum; Polymerase chain reaction; Psychological aspects; Renal Dialysis - adverse effects; Renal failure; Reverse transcription; Signal Transduction - drug effects; Smooth muscle; TLR4 protein; Toll-like receptor 4; Toll-Like Receptor 4 - genetics; Toll-like receptors; Transcription factors; Vimentin; Vimentin - genetics; Western blotting; United States > US; China
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2016.5744

Peritoneal dialysis (PD)-associated peritoneal fibrosis is a serious complication in patients with chronic renal failure on dialysis maintenance. Studies have shown that patients on long-term PD have chronic inflammation. The epithelial-to-mesenchymal transition (EMT) induced by inflammation is a major cause of peritoneal fibrosis and dysfunction. As a potent antioxidant property, melatonin has an antifibrotic effect. The present study investigated the effects of melatonin on lipopolysaccharide (LPS)-induced EMT and examined the molecular mechanisms in peritoneal mesothelial cells using western blotting, reverse transcription-polymerase chain reaction and immunofluorescence staining. The results of the study found that melatonin inhibited LPS-induced morphological changes, decreased the expression of LPS-induced markers of EMT, including vimentin and α-smooth muscle actin, and increased the expression of E-cadherin. In addition, it was found that the action of melatonin was mediated through the inactivation of the Toll-like receptor (TLR)4/c-Jun N-terminal kinase and TLR4/nuclear factor-κB-Snail signaling pathways. Thus, these data provided novel insight into the mechanisms underlying the function of melatonin in peritoneal mesothelial cells during the processes of EMT, and may provide a theoretical basis for the treatment of peritoneal fibrosis.