Plasminogen activator production by human retinal endothelial cells of nondiabetic and diabetic origin.
The authors examined the effect of insulin-like growth factor 1 (IGF 1), epidermal growth factor (EGF), and acidic fibroblast growth factor (AFGF) on the synthesis by human retinal endothelial cell (HREC) of plasminogen activators (PA; tissue-type [t-PA] and urokinase-type [u-PA]) and plasminogen activator inhibitor (PAI). Immunologic and functional assays for t-PA, u-PA, and PA1 were conducted with cell lines derived from three diabetics and three nondiabetic controls. Confluent HREC of nondiabetic origin did not respond to IGF I (100 ng/ml) with any change of t-PA antigen in the medium (10.7 +/- 1.1 ng/ml unstimulated versus 10.1 +/- 0.8 ng/ml) stimulated, P = not significant). Likewise AFGF and EGF caused no significant change of t-PA levels. Both IGF I and EGF caused a significant increase of t-PA from HREC of diabetic origin (9.6 +/- 0.8 ng/ml unstimulated versus 16.6 +/- 1.9 ng/ml IGF I-stimulated, P less than 0.001, and 14.6 +/- 2.7 ng/ml EGF-stimulated P less than 0.005). Supplementation of AFGF had no effect on HREC of diabetic origin. In confluent cultures, only small quantities of u-PA were detected. After wounding confluent cultures, u-PA activity was associated with cells migrating from the wound edges. Functional PA activity was also measured by chromogenic assay. Results further supported a predominance of t-PA activity being produced by confluent HREC in culture. These results suggest that modulation of PA production by HREC is influenced by exposure to growth factors, by the state of confluency, and the origin of the cells (diabetic vesus nondiabetic).
Grant
M B
MB
Department of Medicine, University of Florida College of Medicine, Gainesville 32610-0226.
Guay
C
C
D000368:Aged; D002465:Cell Movement; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000502:physiology; D016220:Fibroblast Growth Factor 1 / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008875:Middle Aged; D010960:Plasminogen Activators / Q000096:biosynthesis*; D015849:Plasminogen Inactivators / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis; D014945:Wound Healing
D015849:Plasminogen Inactivators; D016220:Fibroblast Growth Factor 1; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator