A study of the effects of human blood derivatives and individual growth factors on [3H]thymidine uptake in bovine retinal pericytes and endothelial cells.
Pericytes disappear early, selectively and specifically from retinal capillaries in diabetic microangiopathy, but little is known of their growth and turnover in health and disease. We have studied the effects of human blood derivatives and of a panel of individual growth factors on [3H]thymidine incorporation in bovine retinal pericytes and endothelial cells. Human serum and platelet-rich plasma stimulated incorporation of the nucleotide in a dose-dependent manner in both cell types, and did so more potently than platelet-free plasma. Consistent and significant stimulation of DNA synthesis in pericytes was observed with basic fibroblast growth factor (ED50 = 1.8 x 10(-13) mol/l), acidic fibroblast growth factor (7.4 x 10(-12) mol/l), insulin-like growth factor 1 (8.6 x 10(-10) mol/l), insulin (158 microU/ml) and endothelin-1 (6.1 x 10(-10) mol/l). Transforming growth factor beta 1 inhibited DNA synthesis (ID50 = 3.6 x 10(-10) mol/l) and so did heparin (1.4 x 10(-6) mol/l) and low molecular weight heparin (2.9 x 10(-6) mol/l). Retinal endothelial cells were stimulated by basic fibroblast growth factor (3.2 x 10(-13) mol/l) and acidic fibroblast growth factor (1.3 x 10(-9) mol/l), and inhibited by transforming growth factor beta 1 (1.6 x 10(-12) mol/l). Neither cell type was stimulated by platelet-derived growth factor (A + B chain heterodimer), epidermal growth factor, growth hormone, or nerve growth factor (7S complex). The characteristics and active concentrations of the above growth factors suggest that none is solely responsible for the pericyte mitogenic activity of platelets, serum or plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Dosso
A A
AA
Diabetic Retinopathy Unit, Hammersmith Hospital, London, UK.
Brooks
R A
RA
Beltramo
E
E
Molinatti
P A
PA
Kanse
S M
SM
Kohner
E M
EM
Porta
M
M
D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001790:Blood Physiological Phenomena; D001792:Blood Platelets / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D003956:Dialysis; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010949:Plasma / Q000502:physiology; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D016232:Endothelins; D006133:Growth Substances; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D006493:Heparin; D004247:DNA; D013936:Thymidine