title: Selenium suppresses lipopolysaccharide-induced fibrosis in peritoneal mesothelial cells through inhibition of epithelial-to-mesenchymal transition.
abstract: Peritoneal fibrosis resulting from long-term clinical peritoneal dialysis has been the main reason of dropout from peritoneal dialysis. Peritonitis as a common complication of peritoneal dialysis treatment may lead to the occurrences of peritoneal fibrosis. We cultured peritoneal mesothelial cells with lipopolysaccharides (LPS) in order to stimulate the environment of peritonitis and investigate whether lipopolysaccharides could induce epithelial-to-mesenchymal transition (EMT). Oxidative stress could stimulate fibrogenesis while selenium has antioxidant properties. So, this study also explored whether selenium supplementation affects lipopolysaccharide-induced EMT and fibrosis. We found that lipopolysaccharides could activate EMT changes such as the loss of E-cadherin and the increase of α-smooth muscle actin (α-SMA), collagen I, vimentin, and fibronectin (FN), while selenium inhibits EMT by modulating reactive oxygen species (ROS) generation and ROS/MMP-9 signaling pathways in peritoneal mesothelial cells. Moreover, it was revealed that selenium decreased the EMT events of peritoneal mesothelial cells via inhibition of PI3k/AKT pathways. In conclusion, these findings enable a better understanding of the mechanism of peritoneal fibrosis and explore a new idea for the prevention and treatment.
authors.affiliation: Department of Nephrology, Jining No.1 People's Hospital, Jining, 272100, Shandong, People's Republic of China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.forename: Lingling
authors.initials: L
authors.lastname: Zeng
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.forename: Wanjun
authors.initials: W
authors.lastname: Ren
authors.forename: Chunling
authors.initials: C
authors.lastname: Wu
mesh_terms: D000199:Actins / Q000096:biosynthesis; D002460:Cell Line; D024042:Collagen Type I / Q000096:biosynthesis; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D056627:Peritoneal Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014746:Vimentin / Q000096:biosynthesis
chemical_list: D000199:Actins; D024042:Collagen Type I; D005353:Fibronectins; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D014746:Vimentin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D012643:Selenium