INHIBITION OF MESANGIAL CELL-PROLIFERATION BY PLATELET FACTOR-4

Platelet factor 4 (PF4), an abundant platelet secretory product, is a strong candidate for modulating glomerular pathology, Because PF4 migh t be released from platelets and influence intrinsic cell growth durin g glomerular injury, the effect of PF4 on fetal calf serum- and platel et-derived growth factor (PDGF)-induced mesangial cell mitogenesis was examined, Mitogenesis was measured as the amount of H-3-thymidine inc orporated into acid-precipitable material as well as by autoradiograph y, The effect of PF4 on mesangial cell expression of mRNA for PDGF A c hain and transforming growth factor-beta (TGF-beta(1)) was also examin ed, Fetal calf serum (10%)- and PDGF (10 ng/mL)-stimulated increases i n mesangial cell H-3-thymidine incorporation were inhibited by increme ntal concentrations of PF4 (1 to 25 mu g/mL) showing a maximum reducti on of approximately 80% at 25 mu g/mL of PF4, PF4 was effective when a dded 24 h before and 1, 4, and 8 h, but not 16 h after the addition of PDGF, indicating that inhibition occurred at delayed events in cell-c ycle regulation. PF4 inhibited PDGF-induced increments in mRNA encodin g PDGF A chain and TGF-beta(1). Also, PF4 did not interfere with PDGF receptor binding. The results of this study show that PF4 is a negativ e regulator of mesangial cell proliferation and suggest an interferenc e in cell growth by pathways associated with modulation of the autocri ne growth factors PDGF and TGF-beta(1).