Glucose-based PD solution, but not icodextrin-based PD solution, induces plasminogen activator inhibitor-1 and tissue-type plasminogen activator in human peritoneal mesothelial cells via ERK1/2.
Peritoneal dialysis (PD) solutions containing glucose are considered to cause peritoneal fibrosis. Plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) participate in fibrogenesis of various organs, and human peritoneal mesothelial cells (HPMC) can produce PAI-1 and t-PA following glucose stimulation. Icodextrin has been widely used as an alternative osmotic agent. In this study, we investigated whether icodextrin-based PD solution reduced the production of PAI-1 and t-PA by HPMC. We also examined the involvement of extracellular signal-regulated kinase 1/2 (ERK1/2). Glucose-based PD solutions increased the production of PAI-1 and t-PA by HPMC, whereas icodextrin-based PD solution exerted lesser effects. Glucose-based PD solutions activated ERK1/2, and PD98059 inhibited the production of PAI-1 and t-PA-responses not observed with icodextrin-based PD solution. In conclusion, glucose-based PD solutions, unlike icodextrin-based PD solution, induce overproduction of PAI-1 and t-PA via the ERK1/2 pathway.
Katsutani
Masahira
M
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Ito
Takafumi
T
Masaki
Takao
T
Kohno
Nobuoki
N
Yorioka
Noriaki
N
D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000737:chemistry*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000009:adverse effects; D005936:Glucans / Q000009:adverse effects / Q000737:chemistry; D005947:Glucose / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D000077607:Icodextrin; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*
D015314:Dialysis Solutions; D005419:Flavonoids; D005936:Glucans; D017395:Plasminogen Activator Inhibitor 1; D000077607:Icodextrin; D048052:Mitogen-Activated Protein Kinase 3; D010959:Tissue Plasminogen Activator; D005947:Glucose; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one