The role of protein kinase C activity in the proliferation of peritoneal fibroblasts

Citation
C. Higuchi et H. Nihei, The role of protein kinase C activity in the proliferation of peritoneal fibroblasts, PERIT DIA I, 19, 1999, pp. S353-S357
Citations number
19
Categorie Soggetti
Urology & Nephrology
Journal title
PERITONEAL DIALYSIS INTERNATIONAL
ISSN journal
08968608 → ACNP
Volume
19
Year of publication
1999
Supplement
2
Pages
S353 - S357
Database
ISI
SICI code
0896-8608(1999)19:<S353:TROPKC>2.0.ZU;2-9
Abstract
Objective:To clarify the effect of glucose on peritoneal sclerosis, we perf ormed several experiments to determine how glucose influences the prolifera tion of, and the production of extracellular matrix proteins by, peritoneal fibroblasts. The effect of heparin on these phenomena was also studied. Design: Using rat peritoneal fibroblasts, cells were cultured in four separ ate media: M199 with 5% fetal bovine serum (FBS) (control medium), control medium with 4% glucose (glucose medium), glucose medium with H7 [an inhibit or of protein kinase C (PKC)]50 mu mol, and glucose medium with heparin 50 mu g/mL. Cell proliferation and concentrations of procollagen 3 peptide (P3 P) and hyaluronic acid (HA) in the supernatants were evaluated at 24 hours, 72 hours, and 120 hours after culture. PKC activity in cytosolic and cell membrane fractions were measured 30 minutes after incubation in control med ium and in glucose medium with and without heparin. Results: Glucose accelerated cell proliferation 24 hours after culture, but inhibited it 120 hours after culture. Glucose stimulated the production of HA from these cells 72 hours and 120 hours after culture, but it did not s timulate the production of P3P at any time. Heparin and H7 inhibited cell p roliferation by glucose 24 hours after culture. Heparin and H7 also inhibit ed the production of HA in the peritoneal fibroblasts after culture, but di d not affect the production of P3P. Glucose accelerated PKC activity in cel l membrane, but not in cytosol. Heparin inhibited the elevated PKC activity of the membrane fraction by glucose. Conclusion: Glucose may accelerate the proliferation of, and HA production in, peritoneal fibroblasts by stimulation of cellular PKC activity. Heparin suppresses these phenomena by inhibiting PKC activity.