Platelet-derived growth factor, insulin-like growth factors, fibroblast growth factors and transforming growth factor β do not account for the cell growth activity present in bovine milk

1997 ◽  
Vol 154 (1) ◽  
pp. 45-55 ◽  
Author(s):  
D A Belford ◽  
M-L Rogers ◽  
G L Francis ◽  
C Payne ◽  
F J Ballard ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Growth ◽  
Molecular Mass ◽  
Inhibitory Activity ◽  
Transforming Growth Factor ◽  
Bovine Milk ◽  
3T3 Cells ◽  
Igf I ◽  
Growth Activity

Abstract Cation-exchange chromatography effectively concentrates the cell growth activity present in whey and we have used this process as a basis to characterise further the growth factors present in bovine milk. Under neutral conditions, total bioactivity in the growth factor-enriched cation-exchange fraction chromatographed with an apparent molecular mass of 80–100 kDa. In contrast, acid gelfiltration chromatography resolved two peaks of cell growth activity. A peak at 15–25 kDa contained the bulk of growth activity for Balb/c 3T3 fibroblasts while bioactivity for L6 myoblasts and skin fibroblasts eluted with a molecular mass of 6 kDa. A peak of inhibitory activity for Mv1Lu and MDCK cells also eluted at 15–25 kDa. Both IGF-I and IGF-II were purified from fractions that eluted at 6 kDa, although the IGF peptides alone did not account for the total bioactivity recovered. Platelet-derived growth factor (PDGF), identified by radioreceptor assay, eluted at a slightly higher molecular mass than the peak of growth activity for Balb/c 3T3 cells, and an anti-PDGF antibody was without effect on the growth of Balb/c 3T3 cells in response to the whey-derived factors. Further purification of the inhibitory activity for epithelial cells yielded a sequence for transforming growth factor β (TGF-β), and all inhibitory activity for Mv1Lu cells was immuno-neutralised by an antibody against TGF-β. In contrast, this antibody decreased the growth of Balb/c 3T3 fibroblasts in the whey-derived extract by only 10%. Finally, a cocktail of recombinant growth factors containing IGF-I, IGF-II, PDGF, TGF-β and fibroblast growth factor 2 stimulated growth of Balb/c 3T3 cells to a level equivalent to only 51% of that observed in the milk-derived growth factor preparation. We conclude that: (i) cell growth activity recovered from bovine whey is present in acid-labile high molecular weight complexes; (ii) all cell growth inhibitory activity for epithelial cells can be accounted for by TGF-β; (iii) IGF-I and IGF-II co-elute with the major peak of activity for L6 myoblasts and skin fibroblasts, although the IGF peptides alone do not explain the growth of these cells in the whey-derived extract; and (iv) neither PDGF nor TGF-β account for the 15–25 kDa peak of Balb/c 3T3 growth activity. These data suggest the presence of additional mitogenic factors in bovine milk. Journal of Endocrinology (1997) 154, 45–55

Modulation of growth factor incorporation into ECM of human osteoblast-like cells in vitro by 17 beta-estradiol

1994 ◽  
Vol 267 (6) ◽  
pp. E990-E1001 ◽  
Author(s):  
M. Slater ◽  
J. Patava ◽  
K. Kingham ◽  
R. S. Mason
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Bone Growth ◽  
Transforming Growth Factor ◽  
Bone Matrix ◽  
Tgf Beta ◽  
Subsequent Formation ◽  
Igf I

Human fetal osteoblast-like cells formed a regular multilayered structure in vitro with an extensive collagen-based extracellular matrix. With colloidal gold immunocytochemistry, labels for alkaline phosphatase and osteocalcin were distributed in a relatively diffuse pattern, in contrast to the bone growth factors, insulin-like growth factors I and II (IGF-I and IGF-II), transforming growth factor-beta 1 (TGF-beta 1), and basic fibroblast growth factor, which were colocalized in the collagenous matrix of the multilayer. The inclusion of 17 beta-estradiol (10(-11) to 10(-9) M) in the culture medium increased multilayer depths, increased labeling for IGF-I, IGF-II, and TGF-beta 1, and resulted in earlier detection of TGF-beta 1 label. In contrast, the increase in multilayer depth resulting from treatment with human platelets, an exogenous source of growth factors, was not accompanied by an increase in matrix IGF-I, IGF-II, or TGF-beta 1 label, suggesting a particular effect of estradiol to facilitate this process. Because growth factors in bone matrix may act as coupling agents when released during resorption, reduced growth factor incorporation in the presence of reduced sex steroid concentrations may lead to uncoupling of resorption and subsequent formation.

scholarly journals Periradicular Tissue Responses to Biologically Active Molecules or MTA When Applied in Furcal Perforation of Dogs' Teeth

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Anna Zairi ◽  
Theodoros Lambrianidis ◽  
Ourania Pantelidou ◽  
Serafim Papadimitriou ◽  
Dimitrios Tziafas
Keyword(s):  
Zinc Oxide ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mineral Trioxide Aggregate ◽  
Biologically Active ◽  
Inflammatory Reactions ◽  
Zinc Oxide Eugenol ◽  
Tissue Responses ◽  
Igf I

The aim of this study was the comparative evaluation of inflammatory reactions and tissue responses to four growth factors, or mineral trioxide aggregate (MTA), or a zinc-oxide-eugenol-based cement (IRM) as controls, when used for the repair of furcal perforations in dogs’ teeth. Results showed significantly higher inflammatory cell response in the transforming growth factorβ1 (TGFβ1) and zinc-oxide-eugenol-based cement (IRM) groups and higher rates of epithelial proliferation in the TGFβ1, basic fibroblast growth factor (bFGF), and insulin growth factor-I (IGF-I) groups compared to the MTA. Significantly higher rates of bone formation were found in the control groups compared to the osteogenic protein-1 (OP-1). Significantly higher rates of cementum formation were observed in the IGF-I and bFGF groups compared to the IRM. None of the biologically active molecules can be suggested for repairing furcal perforations, despite the fact that growth factors exerted a clear stimulatory effect on cementum formation and inhibited collagen capsule formation. MTA exhibited better results than the growth factors.

Growth factor stimulated cell proliferation is accompanied by an elevated labile intracellular pool of zinc in 3T3 cells

2002 ◽  
Vol 80 (8) ◽  
pp. 790-795 ◽  
Author(s):  
Shirley C Paski ◽  
Zhaoming Xu
Keyword(s):  
Cell Proliferation ◽  
Growth Factors ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Cell Number ◽  
3T3 Cells ◽  
Intracellular Pool ◽  
Igf I ◽  
Epidermal Growth ◽  
Number Counts

Growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and insulin-like growth factor-I (IGF-I) are required for quiescent 3T3 cells to proliferate, but zinc deprivation impairs IGF-I-induced DNA synthesis. We recently showed that labile intracellular pool of zinc is involved in cell proliferation. Our objective was to determine whether the labile intracellular pool of zinc plays a role in growth factor (PDGF, EGF, and IGF-I) - stimulated proliferation of 3T3 cells. Quiescent 3T3 cells were cultured in DMEM with or without growth factors. Labile intracellular pool of zinc, DNA synthesis, and cell proliferation were assessed using fluorescence microscopy, 3H-thymidine incorporation, and total cell number counts, respectively. After 24 h, growth factors stimulated DNA synthesis (24%) but not cell proliferation. After 48 h, growth factors stimulated both DNA synthesis (37%) and cell proliferation (89%). In response to growth factor stimulation, the labile intracellular pool of zinc was also elevated after 24 or 48 h of treatment. In summary, growth factor (PDGF, EGF, and IGF-I) - stimulated increase in DNA synthesis and cell proliferation were accompanied by an elevated labile intracellular pool of zinc in 3T3 cells. Since elevation of the labile intracellular pool of zinc occurred along with increased DNA synthesis, but cell proliferation remained unchanged, the elevation of the labile intracellular pool of zinc likely occurred during the S phase to provide the zinc needed to support DNA synthesis and ultimately cell proliferation.Key words: PDGF, EGF, IGF-I, labile intracellular pool of zinc, cell proliferation, DNA synthesis, 3T3 cells.

Transforming growth factor β in bovine milk: concentration, stability and molecular mass forms

1996 ◽  
Vol 151 (1) ◽  
pp. 77-86 ◽  
Author(s):  
M-L Rogers ◽  
C Goddard ◽  
G O Regester ◽  
F J Ballard ◽  
D A Belford
Keyword(s):  
Growth Factor ◽  
Molecular Mass ◽  
Transforming Growth Factor ◽  
Bovine Milk ◽  
Gel Filtration ◽  
Transforming Growth Factor Β ◽  
Exchange Chromatography ◽  
Epithelial Cell Line ◽  
Acid Activation ◽  
Chromatographic Procedure

Abstract Transforming growth factor β (TGF-β) is one of the predominant growth factors present in milk. The concentration, molecular mass forms and stability of TGF-β in bovine milk were investigated using a standard bioassay measuring the growth inhibition of a mink lung epithelial cell line. Most of the TGF-β bioactivity in milk was found to be in a latent form, which was also retained in the whey fraction. After acid activation, the total TGF-β concentration was 4·3 ± 0·8 ng and 3·7 ± 0·7 ng TGF-β per ml of milk and cheese whey respectively. Cation-exchange chromatography at pH 6·5 was used to concentrate latent whey-derived TGF-β, which could be activated by transient exposure to extremes of pH, urea or heat. Heparin did not significantly activate milk-derived TGF-β. Neutral gel filtration of the cationic whey fraction revealed a major peak of latent TGF-β with a molecular mass of 80 kDa and a smaller peak at 600 kDa. Transient acidification of the cationic whey fraction prior to neutral gel filtration, or gel filtration under acidic conditions, released low molecular mass TGF-β from both high molecular mass peaks. Whey-derived TGF-β was purified using a five-step chromatographic procedure. An N-terminal sequence was obtained for TGF-β2, which accounted for over 85% of the TGF-β bioactivity in whey. All TGF-β activity in whey could be neutralised by a monoclonal antibody directed against TGF-β1, -β2 and -β3. The results suggest that the majority of TGF-β in bovine milk is present in a small latent complex. Journal of Endocrinology (1996) 151, 77–86

Profile of IGF-binding proteins secreted by intestinal epithelial cells changes with differentiation

1994 ◽  
Vol 267 (5) ◽  
pp. G843-G850 ◽  
Author(s):  
S. Oguchi ◽  
W. A. Walker ◽  
I. R. Sanderson
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Binding Proteins ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Intestinal Epithelial Cells ◽  
Alpha Activity ◽  
Intestinal Epithelial ◽  
Igf I

Previous reports have shown that gastrointestinal epithelial cells produce insulin-like growth factor-binding proteins (IGF-BP), which modulate the actions of IGF. This study aims to examine the relationship between differentiation and IGF-BP secretion by human intestinal epithelial cells and the effect of growth factors on their production. Caco-2 cells were cultured in serum-free media. IGF-BP secretion into the incubation media was analyzed by Western ligand blotting and immunoblotting. Caco-2 cells produced IGF-BP-2, IGF-BP-3, and IGF-BP-4. Secretion of IGF-BP-2 and IGF-BP-3 increased with differentiation, but IGF-BP-4 secretion diminished. The effect of exogenous growth factors on IGF-BP secretion was maximal at earlier stages of differentiation. IGF-I stimulated mainly IGF-BP-3 production, but epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) stimulated predominantly IGF-BP-4 secretion. Adding an anti-EGF receptor antibody to block autocrine TGF-alpha activity inhibited IGF-BP-4 production but stimulated IGF-BP-2 and IGF-BP-3. In conclusion, the profile of IGF-BP secretion changes with differentiation. IGF-I and EGF (or TGF-alpha) stimulate different types of IGF-BP, with autocrine TGF-alpha activity being a factor affecting IGF-BP production during differentiation.

scholarly journals Gastrointestinal growth factors and pancreatic islet hormones during postoperative IGF-I supplementation in man

2000 ◽  
Vol 167 (2) ◽  
pp. 331-338 ◽  
Author(s):  
T Leinskold ◽  
TE Adrian ◽  
U Arnelo ◽  
J Larsson ◽  
J Permert
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Abdominal Surgery ◽  
Pancreatic Islet ◽  
Plasma Levels ◽  
Transforming Growth Factor ◽  
Gastrointestinal Hormones ◽  
Pancreatic Glucagon ◽  
Islet Hormones ◽  
Igf I

Insulin-like growth factor-I (IGF-I) has been demonstrated to exert a nitrogen sparing effect, both experimentally and in patients after abdominal surgery. IGF-I is a major mediator for the anabolic effects of growth hormone (GH). Whether elevated circulating IGF-I levels are the sole mediator of the anabolic effects following GH has not been clarified. IGF-I influences glucose metabolism, both through its own specific receptor and by activating the insulin receptor, and has also been proposed to influence pancreatic islet secretion directly. In the present study, the postoperative effects of IGF-I on plasma levels of other gastrointestinal and pancreatic islet hormones and growth factors were measured in patients after abdominal surgery. Fifteen patients who were candidates for large bowel resection were randomly divided into two groups: IGF-I-treated (n=8) and placebo-treated (n=7). The IGF-I group received daily two s.c. injections of human recombinant IGF-I (80 microg/kg body weight) for five days, beginning on the morning of the first postoperative day. The other group received placebo injections. Fasting plasma levels of gastrointestinal growth factors (epidermal growth factor, transforming growth factor-alpha, IGF-II), gastrointestinal hormones (gastrin, enteroglucagon, peptide YY), and islet hormones (insulin, islet amyloid polypeptide (IAPP) and pancreatic glucagon) were determined by RIA preoperatively and after five days of treatment. No significant effects of IGF-I on other growth factors or gastrointestinal hormones were seen. A marked increase in plasma insulin postoperatively compared with the preoperative levels (42+/-3 vs 61+/-5 pM, P<0.05) was seen in the placebo group, whereas the postoperative levels in the IGF-I-treated patients remained unchanged (44+/-3 vs 45+/-4 pM). A similar pattern was observed for IAPP and cortisol concentrations. No differences in glucagon concentrations were seen. In conclusion, these results suggest that IGF-I does not influence production of other gastrointestinal hormones thought to be involved in alimentary growth or pancreatic glucagon. In contrast, IGF-I caused a marked reduction of insulin and IAPP secretion. The inhibition of beta-cell secretion could be direct or, alternatively, could involve an improvement in postoperative insulin resistance, perhaps by reducing serum cortisol.

Regulation of DNA synthesis in chicken adipocyte precursor cells by insulin-like growth factors, platelet-derived growth factor and transforming growth factor-β

1991 ◽  
Vol 131 (2) ◽  
pp. 203-209 ◽  
Author(s):  
S. C. Butterwith ◽  
C. Goddard
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Transforming Growth Factor ◽  
Precursor Cells ◽  
Igf I ◽  
Tgf Β1 ◽  
Adipocyte Precursor ◽  
Insulin Like Growth Factors

ABSTRACT Adipose tissue growth can occur by both hypertrophy and hyperplasia. The capacity for adipocyte hyperplasia in vivo resides in a population of fibroblast-like adipocyte precursor cells but the regulation of the proliferation of these cells by growth factors has not been well characterized. This study was designed to determine the effects of the insulin-like growth factors (IGF-I and IGF-II), platelet-derived growth factor (PDGF) and transforming growth factor-β1 (TGF-β1) added alone or together on the proliferation of primary adipocyte precursor cells in vitro. Adipocyte precursor cell proliferation measured by [3H]thymidine incorporation into DNA was stimulated by all of these growth factors and was particularly marked with PDGF. IGF-I or IGF-II added together with TGF-β1 produced a greater than additive response and the effect of PDGF was synergistic with that of IGF-I at certain concentrations. Stimulation of proliferation of some cell types by TGF-β has been linked to the secondary production of PDGF but the evidence we have suggests that this is unlikely in chicken adipocyte precursors. DNA synthesis in response to TGF-β1 required only a short exposure to the peptide, and conditioned medium from chicken adipocyte precursor cells previously exposed to TGF-β had no effect on DNA synthesis when added to fresh batches of cells. Addition of TGF-β1 together with PDGF produced a synergistic effect whereas an additive effect would be expected if PDGF mediated the effect of TGF-β1. IGF-I mRNA is expressed in the Ob 1771 preadipocyte cell line during differentiation, in stromalvascular cells from adipose tissue, and TGF-β mRNA is expressed in both proliferating and differentiating 3T3-L1 preadipocytes. Together with the data presented here, this would indicate that these peptides have a role in adipocyte development by an autocrine or paracrine mechanism although the source of PDGF in vivo is at present unknown. Journal of Endocrinology (1991) 131, 203–209

Growth Factors in Human Ovarian Follicle Fluid and Growth Factor Receptors in Granulosa-Luteal Cells

1995 ◽  
Vol 10 (4) ◽  
pp. 216-220 ◽  
Author(s):  
R. McWilliam ◽  
R.E. Leake ◽  
J.R.T. Coutts
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
In Vitro Fertilisation ◽  
Luteal Cells ◽  
Igf I ◽  
Follicular Fluids

The levels of oestradiol (E2), progesterone (P4), transforming growth factor a (TGFa), transforming growth factor β2 (TGFβ2), insulin-like growth factor I (IGF-I), platelet-derived growth factor AB (PDGF-AB) and epidermal growth factor (EGF) were measured in follicular fluids obtained from patients undergoing ovarian stimulation as part of an in vitro fertilisation program. Each of the substances was detected in all of the fluid samples tested, except TGFα (which was detected in 90% of samples tested), PDGF-AB (70%) and EGF (2%). Comparisons were made between each of these factors, follicular maturity, successful oocyte recovery and the outcome of fertilisation and embryo transfer. No statistically significant correlations were found. The presence of receptors for EGF, IGF-I and PDGF in extracts from granulosa-luteal cells isolated from follicular fluids was detected by means of Western blotting. The co-localisation of these growth factors and their receptors within the ovarian follicle suggests a likely role in control of follicular development.

Effects of hormones and growth factors on TGF-β1 expression in bovine mammary epithelial cells

2005 ◽  
Vol 72 (1) ◽  
pp. 39-48 ◽  
Author(s):  
Joanna Zarzyńska ◽  
Małgorzata Gajewska ◽  
Tomasz Motyl
Keyword(s):  
Cell Cycle ◽  
Mammary Gland ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mammary Epithelial ◽  
Inhibition Of Proliferation ◽  
Igf I ◽  
Induction Of Apoptosis ◽  
Tgf Β1

The decline of mammary epithelial cell (MEC) number during mammary gland involution in the cow is due to inhibition of proliferation and induction of apoptosis. Transforming growth factor-beta 1 (TGF-β1) belongs to a group of intramammary auto/paracrine inhibitors of bovine MEC growth and inducers of apoptosis. However, the mechanism responsible for the regulation of TGF-β1 expression in MEC is not known. The present study examined the effect of the hormones, growth hormone (GH), somatostatin (STS), 17-β oestradiol (E2), progesterone (P4), as well as the growth factors, insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF), on TGF-β1 expression in the bovine MEC lines, BME-UV1 and MAC-T. The model of apoptosis in bovine mammary gland in vitro was applied by reduction of fetal bovine serum (FBS) (from 10% to 2% or 0·5% FBS) in the cell environment to show the relationship between TGF-β1 expression and apoptosis in bovine MEC. RT-PCR, Western blot and laser scanning cytometry (LSC) were used for analysis of TGF-β1 transcript and protein level as well as apoptosis and cell cycle in examined MEC. In this model of apoptosis, FBS deficiency (mimicking the naturally occurring decline in the access of bioactive compounds and nutrients at the end of lactation and dry period) was associated with increased TGF-β1 expression at the level of transcript and protein, induction of apoptosis and inhibition of cell cycle. Exogenous TGF-β1, IGF-I, EGF and GH inhibited FBS-deficiency-stimulated TGF-β1 expression. The suppressive effect of GH was reversed when cells were maintained longer in FBS-deficient medium. In general, STS, E2 and P4 increased TGF-β1 expression. However, this effect was dependent on hormone concentration and cell line. BME-UV1 cells were much more responsive to the peptides, GH, STS, IGF-I and EGF, whereas MAC-T cells were more responsive to the steroid sex hormones: E2 and P4.

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