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Query: UNIPROT:P00750 (
PLA
)
16,800
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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).
...
PMID:Plasminogen activator production by human retinal endothelial cells of nondiabetic and diabetic origin. 170 73
The migration of retinal pigment epithelial (RPE) cells from their normal anatomic position to a new position in the vitreous cavity is a critical feature of proliferative vitreous retinopathy. To determine if insulin-like growth factor I (
IGF I
), which is present in the vitreous fluid of diabetics, stimulates RPE cells, we examined the effects of
IGF I
on the proliferation, chemotaxis, and release of
plasminogen activator
by these cells. At the concentrations of
IGF I
tested, significant proliferation of RPE cells is seen. Significant chemotaxis of the RPE cells also is seen at all the concentrations of
IGF I
tested. The mean number of migrating cells per high-powered field in control studies was 43 +/- 13 (x +/- SEM), and for
IGF I
at 2.5 ng and 50 ng/ml the mean numbers of migrating cells were 96 +/- 17 and 483 +/- 62, respectively (P less than 0.001 for each comparison). The
IGF I
response was noted to be dose-dependent. The chemotactic response noted at 50 ng/ml of
IGF I
was greater than the positive chemotactic control of 10% fetal calf serum. Addition of alpha IR-3, an
IGF I
receptor antibody, eliminated the
IGF I
chemotactic response. The effect of
IGF I
on the secretion of plasminogen activators was assessed using an immunological assay for
tissue-type plasminogen activator
(t-PA) and plasminogen activator inhibitor (PAI). Media conditioned by RPE cells have measureable levels of PAI and t-PA antigen.
IGF I
supplementation resulted in an increase of t-PA secretion and PAI secretion over basal levels. These studies support a role for
IGF I
in modulating RPE cell function.
...
PMID:Insulin-like growth factor I stimulates proliferation, migration, and plasminogen activator release by human retinal pigment epithelial cells. 211 Dec 35
