Effect of prednisolone on increased expression of laminin by human peritoneal mesothelial cells cultured with high glucose.
This study aimed to clarify the role of laminin (a component of the extracellular matrix) in the mechanism of peritoneal fibrosis in continuous ambulatory peritoneal dialysis (CAPD) patients, and the effect of prednisolone on such fibrosis. We used semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and ELISA to study laminin mRNA expression and laminin protein production by human peritoneal mesothelial cells (HPMCs) cultured under various conditions. After 6 hours, medium 199 with a high glucose content (4.0%) increased laminin mRNA expression by 1.38-fold relative to control medium (0.1% glucose). Prednisolone (1 mumol/L) suppressed this increase by 92.9%. The laminin protein level in culture supernatant was increased 1.83-fold after incubation for 24 hours in high-glucose medium. Prednisolone (1 mumol/L) suppressed this increase by 58.3%. The effects of prednisolone were prevented by a glucocorticoid receptor antagonist (RU486) at 100 mumol/L. We conclude that culture of HPMCs in high-glucose medium increases laminin mRNA and protein expression, while prednisolone suppresses these changes via the glucocorticoid receptor, suggesting that prednisolone may prevent peritoneal fibrosis in CAPD patients.
Ogata
S
S
Second Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan.
Yorioka
N
N
D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism*; D005355:Fibrosis; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D011239:Prednisolone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003470:Culture Media; D007797:Laminin; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D011239:Prednisolone; D005947:Glucose