Regulation of insulin-like growth factor binding protein synthesis and secretion in XXXX retinal pigment epithelial cells.

@entity1 @entity19518 @entity2301 @entity442 @entity2856 @entity1928
Cultured @entity1 retinal pigment epithelial cells (RPE) secrete insulin-like growth factor binding proteins (IGFBPs), a family of polypeptides which modulate the actions of the insulin-like growth factors. RPE cells secrete two IGFBPs with Mr estimates of 34,000 and 46,000, respectively. Treatment of RPE cells with @entity442 markedly stimulated the secretion of the 46,000 Mr form. This stimulation occurred via an @entity2856 independent mechanism because both [QAYL] @entity442 (an @entity442 analogue with decreased affinity for the IGFBPs but normal affinity for the @entity2856 ) and alpha-IR3 (a blocking monoclonal antibody against the @entity2856 ) had no effect on @entity442 stimulated increases in IGFBPs. Additionally, [QAYL] @entity442 enhanced RPE cell proliferation to the same magnitude as @entity442 . Treatment with @entity442 , [QAYL] @entity442 , or alpha-IR3 had no effect on steady-state levels of the 2.5 kb @entity2301 or the 1.3 kb @entity19518 mRNA transcripts as measured by Northern blotting and quantitative autoradiography. @entity1928 and a group of candidate growth factors, including platelet-derived growth factor, epidermal growth factor, and acidic and basic fibroblast growth factor, modestly increased IGFBP secretion when compared to untreated cells, but these effects were small when compared to @entity442 treatment. Fetal calf serum enhanced the presence of the 2.5 kb @entity2301 mRNA transcript in a dose-dependent fashion but had no effect on the 1.3 kb @entity19518 mRNA transcript. @entity442 , @entity1928 , and the candidate growth factors had no effect on either @entity2301 or @entity19518 mRNA. These data suggest that the production of IGFBPs in @entity1 RPE cells is regulated by distinct mechanisms which include (1) an @entity2856 independent interaction of @entity442 with secreted IGFBPs and (2) de novo synthesis of IGFBPs by serum-containing factors.
