Korean J Nephrol.  2000 May;19(3):401-409.

Effect of Heparin on the Production of Fibronection in Cultured Human Peritoneal Mesothelial Cells

• Yang WS
• Kim SB
• Kim BS
• Lee SK
• Park JS

Abstract

Interleukin-1beta(IL-1beta), which is released into the peritoneal cavity during peritonitis in continuous ambulatory peritoneal dialysis(CAPD) patients, stimulates the production of extracellular matrix proteins, including fibronectin and type, I collagen, in the cultured peritoneal mesothelial cells(HPMCs). This may participate in the development of peritoneal fibrosis developing after episodes of peritonitis. Heparin stimulates the fibrinolysis and it is a routine practice to put 0.5-1U/mL of heparin into the dialysis fluid to prevent the formation of fibrin clot. Besides the anticoagulant acivity, heparin has diverse biologic effects on the cells. In this study, we investigated the effect of heparin on the production of fibronectin, one of the extracellular matrix proteins, in the cultured human peritoneal mesothelial cells. Incubation of the cultured HPMCs with IL-1beta(1 ng/mL) caused an increased expression of fibronectin mRNA by the cells. This stimulatory effect of IL-18 on the expression of fibronectin mRNA was inhibited by heparin, dose-dependently as well as time-dependently. The expression of fibronectin mRNA in the unstimulated cells was also inhibited by heparin. The amount of secreted fibronectin in the culture supernatant was decreased by heparin(1U/mL). This inhibitory effect was present regardless of the addition of IL-lbeta. However, IL-lbeta-induced increase in the expression of TGF bata1 mRNA in the cultured HPMCs was not inhibited by heparin. In conclusion, heparin inhibited the production of fibronectin by the cultured HPMCs at the concentration used clinically during peritonitis in CAPD patients. This suggests that heparin may have a preventive effect on the development of peritonitis associated peritoneal fibrosis as well as decrease the formation of fibrin clot.

Keyword

Peritoneal mesothelial cell; Heparin; Fibronectin; Interleukin-1beta

MeSH Terms

Collagen
Dialysis
Extracellular Matrix Proteins
Fibrin
Fibrinolysis
Fibronectins
Heparin*
Humans*
Interleukin-18
Interleukin-1beta
Peritoneal Cavity
Peritoneal Dialysis, Continuous Ambulatory
Peritoneal Fibrosis
Peritonitis
RNA, Messenger
Collagen
Extracellular Matrix Proteins
Fibrin
Fibronectins
Heparin
Interleukin-18
Interleukin-1beta
RNA, Messenger