Inhibition of mesangial cell proliferation by platelet factor 4

Jeffrey L. Barnes, Katherine A. Woodruff, Shirley P. Levine, Hanna E. Abboud

Research output: Contribution to journalArticle

13 Scopus citations

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 languageEnglish (US)
Pages (from-to)991-998
Number of pages8
JournalJournal of the American Society of Nephrology
Volume7
Issue number7
StatePublished - Jul 1 1996

Keywords

  • Mesangial cells
  • Platelet factor 4
  • Platelet-derived growth factor
  • Proliferation

ASJC Scopus subject areas

  • Nephrology

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