Retinoids increase urokinase-type plasminogen activator production by human retinal pigment epithelial cells in culture.
OBJECTIVE
To examine the effect of two retinoids, all-trans-retinoic acid (tretinoin) and all-trans-9-(4-methoxy-2,3,6- trimethylphenyl)-3,7-dimethyl- 2,4,6,8-nonatetraenoic acid (acitretin) on the production of plasminogen activators and plasminogen activator inhibitors by human retinal pigment epithelial cells in culture.


METHODS
Cultures of human retinal pigment epithelial cells were incubated with either of the retinoids at a concentration of 1 microM for 24-72 hours. The media were assayed using solid-phase immunocapture assays and zymography.


RESULTS
Both retinoids caused a twofold to sevenfold increase in urokinase-type plasminogen activator in the medium. The effect was seen after 24 hours in culture and was further augmented up to 72 hours. No significant amounts of tissue-type plasminogen activator were detected. The plasminogen activator inhibitor activity was unaffected by the retinoids. Proliferation and morphology of retinal pigment epithelial cells were also unaffected by the retinoids in incubations for up to 72 hours.


CONCLUSIONS
Retinoids profoundly affect the extracellular proteolysis of retinal pigment epithelial cells in culture. This effect may be related to the differentiation-inducing activity of retinoids seen in other cell types, often connected with changes in extracellular proteolysis. It is possible that retinoids may modulate dedifferentiation, proliferation, and migration of retinal pigment epithelial cells seen in vitro, as well as in the pathogenesis of retinal disease.
Immonen
I
I
Department of Ophthalmology, University of Helsinki, Finland.
Sirén
V
V
Stephens
R W
RW
Liesto
K
K
Vaheri
A
A
D017255:Acitretin / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007118:Immunoassay; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D015849:Plasminogen Inactivators / Q000096:biosynthesis; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
D015849:Plasminogen Inactivators; D014212:Tretinoin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D017255:Acitretin