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

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 ma...

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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
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1791-2997 1791-3004
DOI:	10.3892/mmr.2016.5744