Abstract
Platelet factor 4 (PF4), an abundant platelet secretory product, is a strong candidate for modulating glomerular pathology. Because PF4 might be released from platelets and influence intrinsic cell growth during glomerular injury, the effect of PF4 on fetal calf serum- and platelet-derived growth factor (PDGF)-induced mesangial cell mitogenesis was examined. Mitogenesis was measured as the amount of 3H-thymidine incorporated into acid- precipitable material as well as by autoradiography. The effect of PF4 on mesangial cell expression of mRNA for PDGF A chain and transforming growth factor-beta (TGF-β1) was also examined. Fetal calf serum (10%) and PDGF (10 ng/mL)-stimulated increases in mesangial cell 3H-thymidine incorporation were inhibited by incremental concentrations of PF4 (1 to 25 μg/mL) showing a maximum reduction of approximately 80% at 25 μg/mL of PF4. PF4 was effective when added 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-cycle regulation. PF4 inhibited PDGF-induced increments in mRNA encoding PDGF A chain and TGF-β1. Also, PF4 did not interfere with PDGF receptor binding. The results of this study show that PF4 is a negative regulator of mesangial cell proliferation and suggest an interference in cell growth by pathways associated with modulation of the autocrine growth factors PDGF and TGF-β1.
Original language | English (US) |
---|---|
Pages (from-to) | 991-998 |
Number of pages | 8 |
Journal | Journal of the American Society of Nephrology |
Volume | 7 |
Issue number | 7 |
State | Published - Jul 1996 |
Keywords
- Mesangial cells
- Platelet factor 4
- Platelet-derived growth factor
- Proliferation
ASJC Scopus subject areas
- Nephrology