IGF-binding protein-6 is involved in growth inhibition in SH-SY5Y human neuroblastoma cells: its production is both IGF- and cell density-dependent

1997 ◽  
Vol 152 (2) ◽  
pp. 221-227 ◽  
Author(s):  
S Babajko ◽  
P Leneuve ◽  
C Loret ◽  
M Binoux

Abstract The IGF system is involved in the growth and differentiation of neuroblastoma cells, but the precise roles played by the IGF-binding proteins (IGFBPs) remain unknown. We have examined the expression and functions of IGFBPs produced by the neuroblastoma cell line, SHSY5Y, in the presence of: insulin, IGF-I, IGF-II, des(1–3)IGF-I (an IGF-I analogue with weak affinity for IGFBPs), acidic fibroblast growth factor, basic fibroblast growth factor, or nerve growth factor. Under basal conditions, SH-SY5Y cells in serum-free medium secreted IGF-II, and traces of IGF-I, IGFBP-2 and IGFBP-4. After 24 h of culture, comparative mitogenic potencies were: des(1–3)IGF-I>IGF-1>IGF-II>insulin. After 48 h, when IGFBP-2 and IGFBP-4 concentrations in the culture media had increased, des(1–3)IGF-I remained the most active, but the activity of insulin now equalled or exceeded that of IGF-I and IGF-II. This suggests a negative feedback mechanism involving partial sequestration of IGF-I and IGF-II by IGFBP-2 and IGFBP-4. At high cell density and with high concentrations of IGF-I, des(1–3)IGF-I (40 ng/ml) or IGF-II (80 ng/ml), the mitogenic activities of the IGFs diminished concomitantly with the appearance in the culture medium of an additional IGFBP identified as IGFBP-6, whose production depended on activation of the type 1 IGF receptor. These findings suggest that IGFBP-6 contributes as an autocrine inhibitor in the regulation of growth by the IGF system in these neuroblastoma cells. Journal of Endocrinology (1997) 152, 221–227

1999 ◽  
Vol 162 (1) ◽  
pp. 21-29 ◽  
Author(s):  
P Vendeira ◽  
D Pignatelli ◽  
D Neves ◽  
MM Magalhaes ◽  
MC Magalhaes ◽  
...  

Adrenocortical regeneration after adrenal autotransplantation provides a model for the study of local autocrine/paracrine mechanisms involved in the growth and differentiation of the adrenal cortex. To study the possible involvement of some growth factors, namely basic fibroblast growth factor (bFGF, FGF-2) and insulin-like growth factor I (IGF-I), in cell differentiation, immunohistochemical and ultrastructural studies were carried out on adrenal autotransplants in adult male rats. To distinguish between fasciculata and glomerulosa-like cells with accuracy, tissue sections were immunostained with IZAb, which recognizes the inner zone antigen (IZAg) present in fasciculata and reticularis cells but absent from the glomerulosa, and by electron microscopy. IGF-I-treated animals exhibited a clear glomerulosa-like zone that was devoid of IZAb immunostaining. In this outer subcapsular area, ultrastructural examination showed cells containing mitochondria with irregular cristae resembling those of the fetal or immature glomerulosa cells. In contrast, no significant morphological differences were observed in bFGF-treated animals when compared with those from saline-treated controls, in both of which, IZAb immunostaining occurred in almost all adrenocortical cells, with no clear zonation or glomerulosa, as seen in the intact animal. Plasma aldosterone and corticosterone concentrations were lower in autotransplanted control animals than in intact controls, although plasma renin activities were similar. IGF-I treatment significantly increased aldosterone concentrations, whereas corticosterone and plasma renin activity were reduced. bFGF infusion further reduced plasma aldosterone, although plasma renin activity and corticosterone were unaffected. These results suggest that the two growth factors have different effects on zonal differentiation and function in the autotransplanted gland. In particular, bFGF, by reducing glomerulosa function, appears partly to replicate the actions of ACTH in normal animals. In contrast, IGF-I enhances the glomerulosa secreting phenotype and diminishes that of the fasciculata/reticularis, possibly replicating the actions of angiotensin II or a low sodium diet.


1997 ◽  
Vol 272 (2) ◽  
pp. E297-E303 ◽  
Author(s):  
Y. Chen ◽  
B. Gustafsson ◽  
H. J. Arnqvist

Because the locally produced insulin-like growth factor-binding proteins (IGFBP) may influence bladder hypertrophy, either directly or by their interaction with insulin-like growth factor I (IGF-I), we studied the IGF system during the development of urinary bladder hypertrophy in rats with streptozotocin-induced diabetes. Messenger RNA for IGF-I, IGFBP-2, and IGFBP-4 was determined by solution hybridization. The bladder wet weight was elevated after 7 days. DNA synthesis was increased and peaked at 2 days, whereas DNA content per bladder wet weight was decreased by 7 days. The IGF-I mRNA did not change during the first 7 days and then decreased, and IGFBP-4 mRNA was increased transiently on day 7. On the other hand, IGFBP-2 mRNA was significantly increased after 1 day (2-fold), peaked by 7 days (6.4-fold), and then declined to approximately 50% above control at the end of experiment. This was associated with an increased IGFBP-2 protein content. Our results suggest that both stretching of the bladder due to diuresis and the diabetic state contribute to changes of the IGF system in the hypertrophying bladder.


2020 ◽  
Vol 21 (10) ◽  
pp. 3698 ◽  
Author(s):  
Takato Hara ◽  
Shiori Yabushita ◽  
Chika Yamamoto ◽  
Toshiyuki Kaji

Syndecan-4 is a member of the syndecan family of transmembrane heparan sulfate proteoglycans, and is involved in cell protection, proliferation, and the blood coagulation-fibrinolytic system in vascular endothelial cells. Heparan sulfate chains enable fibroblast growth factor-2 (FGF-2) to form a complex with its receptor and to transduce the cell growth signal. In the present study, bovine aortic endothelial cells were cultured, and the intracellular signal pathways that mediate the regulation of syndecan-4 expression in dense and sparse cultures by FGF-2 were analyzed. We demonstrated the cell density-dependent differential regulation of syndecan-4 expression. Specifically, we found that FGF-2 upregulated the synthesis of syndecan-4 in vascular endothelial cells via the MEK1/2-ERK1/2 pathway in dense cell cultures, with only a transcriptional induction of syndecan-4 at a low cell density via the Akt pathway. This study highlights a critical mechanism underlying the regulation of endothelial cell functions by proteoglycans.


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