Cytokines modulate the sensitivity of human fibroblasts to stimulation with insulin-like growth factor-I (IGF-I) by altering endogenous IGF-binding protein production

1993 ◽  
Vol 137 (1) ◽  
pp. 151-159 ◽  
Author(s):  
M. E. Yateman ◽  
D. C. Claffey ◽  
S. C. Cwyfan Hughes ◽  
V. J. Frost ◽  
J. A. H. Wass ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Human Fibroblasts ◽  
Dermal Fibroblasts ◽  
Insulin Like Growth Factor ◽  
Tnf Α ◽  
Igf I ◽  
Dose Dependent ◽  
Tgf Β1 ◽  
Igfbp 3

ABSTRACT Human dermal fibroblasts produce a number of insulin-like growth factor-binding proteins (IGFBPs) including the main circulating form, IGFBP-3. It has been suggested that the regulation of IGFBP secretion may play a major role in modulating insulin-like growth factor (IGF) bioactivity. We have quantified the effects of two cytokines, transforming growth factor-β1 (TGF-β1) and tumour necrosis factor-α (TNF-α) which have opposing actions on fibroblast IGFBP-3 production, and examined their subsequent role in IGF-I mitogenesis. TGF-β1 caused a dose-dependent increase in IGFBP-3 in serum-free fibroblast-conditioned media. TGF-β1 (1 μg/l) resulted in immunoreactive IGFBP-3 levels reaching 286·5 ± 22·4% of control after 20 h, the increase being confirmed by Western ligand blot. TNF-α caused a dose-dependent decrease in fibroblast IGFBP-3 secretion, 1 μg TNG-α/l reducing IGFBP-3 levels to 32·1 ± 11·% of control. This effect was not due to cytotoxicity and was not cell-density-dependent. Fibroblast proliferation was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric cytochemical bioassay. The addition of IGF-I resulted in dose-dependent growth stimulation after 48 h, the effective range being 20–100 μg/l. The IGF-I analogue Long-R3-IGF-I which has little affinity for the IGFBPs was approximately 20-fold more potent in this assay, and was unaffected by exogenous IGFBP-3. While the addition of 1 μg TGF-β1/l to increasing doses of IGF-I resulted in a fourfold decrease in mitogenic sensitivity to the IGF-I, no such effect was seen with Long-R3-IGF-I. Conversely, 1 μg TNF-α/l increased fibroblast IGF-I sensitivity five-fold, an effect not observed with the IGF-I analogue. Such data suggest that endogenous IGFBP-3 inhibits IGF-I bioactivity and that the regulation of IGF mitogenesis by TGF-β1 and TNF-α can occur via local IGFBP modulation. This may represent a mechanism by which complex growth signals are co-ordinated in vivo. Journal of Endocrinology (1993) 137, 151–159

scholarly journals IGFBP-3 and IGFBP-5 production by human intestinal muscle: reciprocal regulation by endogenous TGF-β1

1998 ◽  
Vol 275 (6) ◽  
pp. G1282-G1290 ◽  
Author(s):  
Toni L. Bushman ◽  
John F. Kuemmerle
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Muscle Cells ◽  
Transforming Growth Factor Β1 ◽  
Receptor Interaction ◽  
Pcr Analysis ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Tgf Β1 ◽  
Igfbp 3

Insulin-like growth factor-I (IGF-I)-mediated growth of cells can be modulated by specific IGF binding proteins (IGFBPs) that inhibit or augment IGF-I ligand-receptor interaction. IGFBP expression and production by human intestinal muscle cells in culture was characterized in rapidly growing cells ( day 3 of culture), in confluent cells ( day 7), and in postconfluent cells ( day 14). RT-PCR analysis identified IGFBP-3, IGFBP-4, and IGFBP-5 mRNA during all three phases of growth. The production of IGFBP-3 and IGFBP-5 was regulated in reciprocal fashion. IGFBP-5 production was high on day 3and decreased two- to fivefold by day 14, and IGFBP-3 production was low on day 3and increased five- to eightfold by day 14. IGFBP-4 production remained constant. IGFBP-3 inhibited and IGFBP-5 augmented IGF-I-induced proliferation. IGFBP-3 and IGFBP-5 production was regulated in reciprocal fashion by transforming growth factor-β1 (TGF-β1). Immunoneutralization of endogenous TGF-β1 decreased the production of IGFBP-3 and increased the production of IGFBP-5. Addition of exogenous recombinant human TGF-β1 had the opposite effect. We conclude that the expression and time-dependent production of IGFBP-3, IGFBP-4, and IGFBP-5 and their regulation by endogenous TGF-β1 represent mechanisms by which human intestinal muscle cells regulate autocrine IGF-I-mediated growth.

Transforming growth factor β1, pituitary-specifi c transcriptional factor 1 and insulin-like growth factor I gene polymorphisms in the population of the Poltava clay chicken breed: association with productive traits

2015 ◽  
Vol 2 (1) ◽  
pp. 67-72
Author(s):  
R. Kulibaba ◽  
A. Tereshchenko
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Transcriptional Factor ◽  
Meat Production ◽  
Insulin Like Growth Factor ◽  
Chicken Breed ◽  
Igf I ◽  
Productive Traits ◽  
Tgf Β1

Aim. To investigate the gene polymorphisms of transforming growth factor β1 (TGF-β1), pituitary-specifi c transcriptional factor 1 (PIT-1) and insulin-like growth factor I (IGF-I) in the population of Poltava clay chicken breed, used for egg and meat production, and to analyze the association of different genotypes for each locus with productive traits. Methods. Genotyping of the chickens was performed using the polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP). Results. Transforming growth factor TGF-β1, pituitary-specifi c transcriptional factor PIT-1, and insulin-like growth factor IGF-I were shown to be polymorphic in the studied populations. The association between genotypes by the loci TGF-β1 and PIT-1 and the indices of egg and meat production of chickens was demonstrated. Conclusions. The data on the genetic structure of the population of Poltava clay chicken breed by loci TGF-β1 and PIT-1 is recommended for the targeted selection of chickens to produce offspring with desirable genotypes, which will, in addition to classical breeding methods, reveal the productive potential of chickens as effi ciently as possible.

Dexamethasone potentiates the stimulatory effect of insulin-like growth factor-I on collagen production in cultured human fibroblasts

1994 ◽  
Vol 142 (3) ◽  
pp. 571-579 ◽  
Author(s):  
J L E Bird ◽  
J A Tyler
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Human Fibroblasts ◽  
Human Infant ◽  
Insulin Like Growth Factor ◽  
Collagen Production ◽  
Collagen Formation ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Abstract We examined the effects of insulin-like growth factor-I (IGF-I) and dexamethasone on the production of collagen by cultures of human infant foreskin fibroblasts, and the interaction between these two factors. IGF-I at 500 ng/ml maximally increased collagen accumulation fourfold. Collagen was increased twofold relative to total protein production. Dexamethasone at a concentration of 1 μmol/l reduced collagen production by between 25% and 40% in unstimulated cells and those cultured with up to 100 ng IGF-I/ml. However, dexamethasone did potentiate collagen production in cells stimulated with 250 ng IGF-I/ml. This potentiation was independent of any effects of IGF-I or dexamethasone on prostaglandin (PG)E2 production. Transforming growth factor-β (TGF-β) is also a potent stimulator of collagen formation. However, no potentiation of TGF-β-stimulated collagen production by dexamethasone was apparent. The mechanism by which dexamethasone potentiates IGF-I-stimulated collagen production was investigated. Dexamethasone treatment increased IGF-I binding to the type 1 IGF receptor without altering the binding affinity. Dexamethasone also attenuated the secretion of IGF-binding proteins by IGF-I-maintained cells. Journal of Endocrinology (1994) 142, 571–579

scholarly journals Differential Expression of Insulin-Like Growth Factor 1 and Wnt Family Member 4 Correlates With Functional Heterogeneity of Human Dermal Fibroblasts

2021 ◽  
Vol 9 ◽  
Author(s):  
Oliver J. Culley ◽  
Blaise Louis ◽  
Christina Philippeos ◽  
Bénédicte Oulès ◽  
Matthieu Tihy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Family Member ◽  
Transforming Growth Factor ◽  
Dermal Fibroblast ◽  
Smooth Muscle Actin ◽  
Dermal Fibroblasts ◽  
Insulin Like Growth Factor ◽  
Functional Heterogeneity ◽  
Tgf Β1

Although human dermis contains distinct fibroblast subpopulations, the functional heterogeneity of fibroblast lines from different donors is under-appreciated. We identified one commercially sourced fibroblast line (c64a) that failed to express α-smooth muscle actin (α-SMA), a marker linked to fibroblast contractility, even when treated with transforming growth factor-β1 (TGF-β1). Gene expression profiling identified insulin-like growth factor 1 (IGF1) as being expressed more highly, and Asporin (ASPN) and Wnt family member 4 (WNT4) expressed at lower levels, in c64a fibroblasts compared to three fibroblast lines that had been generated in-house, independent of TGF-β1 treatment. TGF-β1 increased expression of C-X-C motif chemokine ligand 1 (CXCL1) in c64a cells to a greater extent than in the other lines. The c64a gene expression profile did not correspond to any dermal fibroblast subpopulation identified by single-cell RNAseq of freshly isolated human skin cells. In skin reconstitution assays, c64a fibroblasts did not support epidermal stratification as effectively as other lines tested. In fibroblast lines generated in-house, shRNA-mediated knockdown of IGF1 increased α-SMA expression without affecting epidermal stratification. Conversely, WNT4 knockdown had no consistent effect on α-SMA expression, but increased the ability of fibroblasts to support epidermal stratification. Thus, by comparing the properties of different lines of cultured dermal fibroblasts, we have identified IGF1 and WNT4 as candidate mediators of two distinct dermal functions: myofibroblast formation and epidermal maintenance.

Comparative study of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) level and ratio measurements and their relationship with an index of clinical activity in the management of patients with acromegaly

Metabolism ◽  
1997 ◽  
Vol 46 (5) ◽  
pp. 494-498 ◽  
Author(s):  
Concepción Páramo ◽  
M.Amalia Andrade O ◽  
Enrique Fluiters ◽  
Reyes Luna ◽  
Javier de la Fuente ◽  
...  
Keyword(s):  
Growth Factor ◽  
Comparative Study ◽  
Binding Protein ◽  
Clinical Activity ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

Specimen processing time and measurement of total insulin-like growth factor-I (IGF-I), free IGF-I, and IGF binding protein-3 (IGFBP-3)

2006 ◽  
Vol 16 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Tiffany G. Harris ◽  
Howard D. Strickler ◽  
Herbert Yu ◽  
Michael N. Pollak ◽  
E. Scott Monrad ◽  
...  
Keyword(s):  
Growth Factor ◽  
Processing Time ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Specimen Processing ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4

1993 ◽  
Vol 136 (1) ◽  
pp. 91-104 ◽  
Author(s):  
L. R. Donahue ◽  
W. G. Beamer
Keyword(s):  
Body Composition ◽  
Growth Factor ◽  
Gh Deficiency ◽  
Body Water ◽  
Insulin Like Growth Factor ◽  
Gh Therapy ◽  
Factor I ◽  
Igf I ◽  
Body Compartments ◽  
Igfbp 3

ABSTRACT Although GH is known to regulate somatic growth during development, its role in regulating adult body composition is less well defined. The effects of GH on individual body compartments – water, fat, protein and mineral – are achieved both by the action of GH and by a GH-induced hormone, insulin-like growth factor-I (IGF-I). We used a genetic model of GH deficiency, the 'little' (gene symbol lit) mouse, to determine the GH regulation of IGF-I and its insulin-like growth factor-binding proteins (IGFBPs) and to define the interaction between these hormones and each body compartment in adults. Our results showed that GH-deficient lit/lit mice had reduced levels of serum IGF-I (range 38–130 μg/l) compared with normal lit/+ littermates (range 432–567 μg/l) between 2 and 52 weeks of age. The lit/lit mice did not experience the fivefold increase in IGF-I between 2 and 4 weeks of age that was seen in lit/+ mice. In lit/lit serum, overall binding of 125I-labelled IGF-I to the four IGFBPs was reduced, solely in response to a reduced amount of IGFBP-3. No overall differences were found between lit/lit and lit/+ mice in the binding of 125I-labelled IGF-I to IGFBP-2, -1 or -4. Age-related declines in IGF-I and IGFBPs were seen in lit/lit mice. However, adult levels of IGF-I were maintained in lit/+ mice to at least 52 weeks of age, as were levels of IGFBP-1 and -4, while IGFBP-3 and -2 declined with age. With respect to body composition, comparison of lit/lit with lit/+ mice showed that the lit/lit mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks onward. These changes occurred despite normal energy intake in lit/lit mice up to 52 weeks of age, indicating that neither undernutrition nor hyperphagia is characteristic of this GH-induced model of obesity. Furthermore, lit/lit males accrued more body fat beginning at an earlier age than lit/lit females. With advancing age, the per cent body fat increased in both lit/lit and lit/+ mice, while the per cent body water and mineral declined. In lit/lit but not lit/+ mice, per cent protein also declined with age. The changes in body water and fat are attributable to lack of adequate GH in the genetically GH-deficient lit/lit mouse. On the other hand, the changes in body protein are more likely to be effects of IGF-I. Changes in mineral observed in lit/lit mice could be the result of action by GH, IGF-I or both hormones. Therefore, when GH is chronically manipulated by GH deficiency as in lit/lit mice, by GH excess as in acromegaly, or by GH therapy, all four body compartments are affected, suggesting that GH therapy is most valuable when the treatment goal is to alter overall body composition. Journal of Endocrinology (1993) 136, 91–104

scholarly journals Genetic Determinants of Circulating Insulin-Like Growth Factor (IGF)-I, IGF Binding Protein (BP)-1, and IGFBP-3 Levels in a Multiethnic Population

2007 ◽  
Vol 92 (9) ◽  
pp. 3660-3666 ◽  
Author(s):  
Iona Cheng ◽  
Katherine DeLellis Henderson ◽  
Christopher A. Haiman ◽  
Laurence N. Kolonel ◽  
Brian E. Henderson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Genetic Determinants ◽  
Igf I ◽  
Igf Binding ◽  
Multiethnic Population ◽  
Igf Binding Protein ◽  
Igfbp 3
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