title: Methylglyoxal and advanced glycation end-products promote cytokines expression in peritoneal mesothelial cells via MAPK signaling.
abstract: BACKGROUND
  Peritoneal dialysis fluid degrades glucose into glucose degradation products that impair peritoneal mesothelial cell functions. These compounds are known to interfere with many cellular functions and to promote the formation of advanced glycation end products (AGEs). This study aimed to investigate the biological effects and the underlying mechanism of glucose degradation products and AGEs on mesothelial cells.
  
  
  METHODS
  Cell proliferation was determined using [3H]-thymidine incorporation assay. Real-time polymerase chain reaction and enzyme linked immunosorbent assay (ELISA) were used to determine the mRNA and protein expression of cytokines. Reactive oxygen species production in mesothelial cells was determined by flow cytometry. Western blot was used to measure the protein expression of p38 MAPK.
  
  
  RESULTS
  Methylglyoxal (MGO) and AGE-human serum albumin (AGE-HSA) inhibited human peritoneal mesothelial cells proliferation in a dose- and time-dependent manner. The mRNA and protein expression of cytokines including vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) was significantly increased after treatment with MGO and AGE-HSA. Also, the antioxidant N-acetylcysteine (NAC) inhibited MGO- or AGE-HSA-induced reactive oxygen species generation. Western blot showed that MGO and AGE increased the phosphorylation levels of p38 MAPK, which was significantly attenuated after treatment of NAC or p38 MAPK inhibitor SB203580. Furthermore, AGE- or MGO-induced increased expression of VEGF and MCP-1 was significantly reduced in the presence of NAC or SB203580.
  
  
  CONCLUSIONS
  Together, this study suggested that AGE or MGO promoted VEGF and MCP-1 expression through activation of p38 MAPK signaling.
authors.affiliation: Department of Nephrology (F-YH), Fujian Provincial Hospital, Fujian Medical University Fuzhou, China; and Department of Nephrology (J-FB, JH, QY, JL), Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Fu-yuan
authors.initials: FY
authors.lastname: Hong
authors.forename: Jin-fang
authors.initials: JF
authors.lastname: Bao
authors.forename: Jing
authors.initials: J
authors.lastname: Hao
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011765:Pyruvaldehyde / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D011725:Pyridines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011765:Pyruvaldehyde; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; C093642:SB 203580; D000111:Acetylcysteine