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Effects of glucose and plasminogen activator inhibitor-1 on collagen metabolism in the peritoneum.

Authors: Higuchi, Chieko  Tanihata, Yoko  Nishimura, Hideki  Naito, Takashi  Sanaka, Tsutomu 
Citation: Higuchi C, etal., Ther Apher Dial. 2005 Apr;9(2):173-81.
Pubmed: (View Article at PubMed) PMID:15828931
DOI: Full-text: DOI:10.1111/j.1774-9987.2005.00232.x

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.

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RGD Object Information
RGD ID: 13208547
Created: 2017-08-11
Species: All species
Last Modified: 2017-08-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.