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Effects of Glucose and Plasminogen Activator Inhibitor‐1 on Collagen Metabolism in the Peritoneum
Author(s) -
Higuchi Chieko,
Tanihata Yoko,
Nishimura Hideki,
Naito Takashi,
Sanaka Tsutomu
Publication year - 2005
Publication title -
therapeutic apheresis and dialysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.415
H-Index - 53
eISSN - 1744-9987
pISSN - 1744-9979
DOI - 10.1111/j.1774-9987.2005.00232.x
Subject(s) - continuous ambulatory peritoneal dialysis , peritoneum , plasminogen activator inhibitor 1 , medicine , endocrinology , plasminogen activator , peritoneal dialysis , tissue inhibitor of metalloproteinase , carbohydrate metabolism , mesothelial cell , fibrosis , glucose uptake , matrix metalloproteinase , pathology , insulin
Nonphysiological solutions containing high glucose levels have been considered an important factor in the etiology of fibrotic changes in long‐term continuous ambulatory peritoneal dialysis (CAPD) patients. At the same time, increased Plasminogen Activator Inhibitor (PAI)‐1 secretion has been reported to correlate with fibrotic changes. We suspected that the high glucose content of peritoneal dialysis solution may induce peritoneal sclerosis via up‐regulation of PAI‐1 gene expression. In this study, we evaluated the effects of glucose on PAI‐1 activity in peritoneal fibrosis in a rat model of CAPD. The effects of glucose on the expressions of PAI‐1 and several other genes correlated with collagen metabolism were also examined in cultured rat peritoneal mesothelial cells and fibroblasts. Sprague‐Dawley rats were intraperitoneally injected twice daily for 28 days with phosphate‐buffered saline (PBS) (control group), PBS containing 4% glucose (glucose group), or PBS containing 4% glucose plus a PAI‐1 inhibitor (PAI‐1 inhibitor group). Thickening of the peritoneum with increase the deposition of collagens type I and III in the submesothelial interstitium were observed in the glucose and the PAI‐1 inhibitor group, but these were less severe in the PAI‐1 inhibitor group. Glucose stimulated expression of the mRNA of PAI‐1, collagen type I and III, and tissue inhibitor of metalloproteinase (TIMP)‐1 in fibroblasts but not in mesothelial cells. Glucose stimulated matrix metalloproteinase (MMP)‐13 mRNA expression in both cell types. The PAI‐1 inhibitor suppressed expression of the mRNAs induced by glucose. In conclusion, glucose induces peritoneal fibrosis, including changes in collagen metabolism, by stimulating PAI‐1 expression.