Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GROWTH”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1998

Chemotaxis of human keratocytes is increased by platelet-derived growth factor-BB, epidermal growth factor, transforming growth factor-alpha, acidic fibroblast growth factor, insulin-like growth factor-I, and transforming growth factor-beta.

PURPOSE: Following corneal wounding, early migration of keratocytes into the wound area is of pivotal importance in the healing process, but the nature of this migration is not well understood. The influence of peptide growth factors on the chemotactic and chemokinetic migration of human corneal keratocytes was investigated, using the following growth factors: platelet derived growth factor-BB (PDGF-BB), epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), and transforming growth factor-beta-1 (TGF-beta 1). METHODS: The chemotactic stimulation was investigated in the Boyden blind-well chemotaxis chamber, and the chemokinetic effect of the growth factors determined by a modified checker-board analysis. RESULTS: PDGF-BB, EGF and TGF-beta 1 stimulated chemotaxis towards a peak value, with a subsequent decline at higher concentrations. PDGF-BB and EGF peaked at 1 ng/ml with a 2.0 and a 2.5-fold increase respectively in the number of keratocytes migrating, whereas TGF-beta 1 reached a maximum response at 0.1 ng/ml, with a 1.7-fold increase. Chemotaxis reached an early plateau and remained constant at concentrations between 1 ng/ml and 100 ng/ml when stimulating with TGF-alpha (2.7-fold), bFGF (2.0-fold), aFGF (2.7-fold), and IGF-I (4.5-fold). Checkerboard analysis revealed that all growth factors were chemotactic agents for human keratocytes, except bFGF, which principally stimulated chemokinesis. CONCLUSION: These in vitro results demonstrate that PDGF-BB, EGF, TGF-alpha, aFGF, IGF-I, and TGF-beta 1 increase keratocyte chemotaxis, and they may play an important role in the early recruitment of keratocytes to the corneal wound site in vivo.

Becaplermin↗
PubMed1997

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

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 gel-filtration 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 bio-activity 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 beta (TGF-beta), and all inhibitory activity for Mv1Lu cells was immunoneutralised by an antibody against TGF-beta. 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-beta 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-beta; (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-beta 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.

3T3 Cells↗
PubMed1996

Hepatocyte growth factor is a novel member of the endothelium-specific growth factors: additive stimulatory effect of hepatocyte growth factor with basic fibroblast growth factor but not with vascular endothelial growth factor.

OBJECTIVE: To seek an endothelium-specific growth factor by examining the mitogenic effects of hepatocyte growth factor (HGF) on endothelial cells and on vascular smooth muscle cells (VSMC). METHODS: Rat and human endothelial cells and VSMC were employed. DNA, RNA and protein synthesis were measured by using [3H]-thymidine, uridine and leucine. Coculture of endothelial cells with VSMC was also performed to study the role of endothelial cells. RESULTS: Coculture of endothelial cells with VSMC resulted in a significant decrease in DNA synthesis of VSMC. HGF, as well as basic fibroblast growth factor (bFGF), stimulated DNA, RNA and protein synthesis by endothelial cells in a dose-dependent manner. Interestingly, co-incubation of endothelial cells with HGF and bFGF resulted in an additive stimulation of DNA synthesis. Similarly, HGF and interleukin-1 alpha and -6 stimulated DNA synthesis by coronary endothelial cells, whereas interleukin-1 beta and transforming growth factor-beta (TGF-beta) did not. However, HGF showed markedly different actions from bFGF on VSMC growth. bFGF, TGF-beta, interleukin-1 alpha, -1 beta and -6 stimulated DNA synthesis in VSMC significantly, whereas HGF did not. Finally, we examined the mitogenic effect of HGF on human aortic endothelial cells and VSMC. Incubation with HGF increased DNA synthesis and growth by endothelial cells in a dose-dependent manner, whose degree was significantly greater than those with bFGF, vascular endothelial growth factor (VEGF) and interleukin-6. Addition of HGF and VEGF showed no additive effect on DNA synthesis in endothelial cells, in contrast to those of bFGF and HGF. On the other hand, bFGF, but not HGF and VEGF, stimulated DNA synthesis in VSMC. CONCLUSION: These results demonstrate that HGF can exert stimulating effects on endothelial cell growth, but not on VSMC growth, in an additive manner with bFGF but not with VEGF. These characteristics of HGF as an endothelium-specific growth factor may provide the opportunity for a new therapeutic strategy for vascular diseases in which the abnormalities were vasoconstriction and pathological growth.

Animals↗
PubMed1997

Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis.

Angiogenesis is a significant prognostic factor in breast cancer, but the factors that control angiogenesis in vivo are not well defined. Multiple angiogenic polypeptides are known, and we have determined the expression of seven of these in primary human breast cancers; the relationship of expression to estrogen receptor and vascular density was also examined. Vascular endothelial growth factor (VEGF) and its four isoforms (121, 165, 189, and 206 amino acids), transforming growth factor (TGF)-beta1, pleiotrophin, acidic and basic fibroblast growth factor (FGF), placental growth factor, and thymidine phosphorylase (platelet-derived endothelial cell growth factor) were quantitated by RNase protection analysis. beta-FGF was also measured by ELISA. The estrogen receptor (ER), epidermal growth factor receptor, and vascular density were analyzed in 64 primary breast cancers. All tumors expressed at least six different vascular growth factors. VEGF was most abundant, and the transcript for the 121-amino acid form predominated. Other angiogenic factors expressed at high levels were thymidine phosphorylase and TGF-beta1. Expression of most of the angiogenic factors did not correlate with that of ER or vascular density. However, thymidine phosphorylase did, with a correlation coefficient of 0.3 (P = 0.03). There were significant associations of pleiotrophin with acidic FGF expression (P = 0.001) and TGF-beta with platelet-derived endothelial cell growth factor expression (P = 0.001). Thus, angiogenesis may involve a coordinate regulation of some vascular growth factors. High VEGF expression correlated with poor prognosis in univariate analysis (P = 0.03), as did ER and epidermal growth factor receptor expression. Basic FGF was also assessed by ELISA and was more highly expressed in tumors than normal breast tissues (median, 346 microg/ml cytosol; range, 54-1323 versus median, 149; range, 32-509; P = 0.01). Implications for therapy are that broad spectrum agents that block features common to these factors may be useful (e.g., antagonism of heparin-binding activity agents), because so many angiogenic factors are expressed. Inhibiting endothelial migration or agents directly toxic to endothelium would be of value in a combined approach to therapy.

Breast Neoplasms↗
PubMed1991

Regulation of rat proximal tubule epithelial cell growth by fibroblast growth factors, insulin-like growth factor-1 and transforming growth factor-beta, and analysis of fibroblast growth factors in rat kidney.

Growth factors may play an important role in regulating the growth of the proximal tubule epithelium. To determine which growth factors could be involved, we have investigated the mitogenicity of various purified factors in rat kidney proximal tubule epithelial (RPTE) cells cultured in defined medium. Fibroblast growth factors, aFGF (acidic FGF) and bFGF (basic FGF), stimulate DNA synthesis in a dose-dependent manner, with ED50 values of 4.5 and 3.2 ng/ml, respectively; their effects are not additive. With cholera toxin in the medium, both aFGF and bFGF can replace insulin or epidermal growth factor (EGF) to attain the maximum level of cell growth, but they cannot replace cholera toxin. Cholera toxin specifically potentiates the effects of FGFs on DNA synthesis. At high cell density, both insulin and insulin-like growth factor 1 (IGF-1) induce DNA synthesis more effectively than EGF, FGFs and cholera toxin. The high concentration (0.2-1.0 microgram/ml) of insulin required for cell growth can be replaced by a low concentration of IGF-1 (10-20 ng/ml), indicating that insulin probably acts through a low affinity interaction with the IGF-1 receptor. Transforming growth factor-beta 1 (TGF-beta 1) inhibits DNA synthesis induced by individual factors and combinations of factors in a concentration-dependent manner. Northern blot analysis shows that mRNA for TGF-beta 1, IGF-1, and aFGF, but not bFGF are present in rat kidney. Western blot analysis and bioassay data confirmed that the majority of FGF-like protein in rat kidney is aFGF. The data suggest that in addition to EGF, IGFs, and TGF-beta, FGFs may also be important kidney-derived regulators of proximal tubule epithelial cell growth in vivo and in vitro.

Animals↗
PubMed1996

Expression of transforming growth factor alpha/epidermal growth factor receptor, hepatocyte growth factor/c-met and acidic fibroblast growth factor/fibroblast growth factor receptors during hepatocarcinogenesis.

It is widely believed that abnormal production of polypeptide growth factors, together with other molecular alterations, play an important role in neoplastic development. Transforming growth factor alpha (TGFalpha), hepatocyte growth factor (HGF) and acidic fibroblast growth factor (aFGF) are the three major growth factors that contribute to liver regeneration occurring via both hepatocyte replication and oval cell proliferation. It is not clear, however, whether and to what extent these growth factors are also involved in hepatocarcinogenesis. In the present study, the gene expression of TGFalpha, HGF and aFGF and their corresponding receptors was examined by Northern blotting and in situ hybridization during hepatocarcinogenesis induced by the Solt-Farber protocol. All three growth factor/receptor systems, TGFalpha/epidermal growth factor receptor (EGFR), HGF/c-met and aFGF/FGF receptors (flg and bek) were significantly elevated at early time points when oval cells were proliferating. Their respective expression decreased after 1 month and remained at a low level until the development of liver tumors. In all hepatocellular carcinomas (HCC) examined, the transcripts of TGFalpha and aFGF were highly expressed, while those of HGF were low. With regard to the receptor expression in the tumors, EGFR was present at varying levels, c-met was expressed at higher levels and flg increased significantly, whereas bek remained at low levels. These data suggest that TGFalpha and aFGF are the major growth factors involved in the progression of HCC, and that the signal of aFGF is mainly transduced by the receptor flg in HCC. Furthermore, HCC cells were phenotypically very similar to oval cells with regard to the gene expression of growth factor/receptor systems. These results, along with the finding that all the HCC cells are positive for the oval cell antigen OV6, and that cytokeratin 19 is heavily expressed in both tumor and oval cells, strongly suggest that at least some of the HCC induced by the Solt-Farber protocol may be derived from oval cells.

Animals↗
PubMed1994

Effect of growth hormone, insulin-like growth factor I, basic fibroblast growth factor, and transforming growth factor beta on cell proliferation and proteoglycan synthesis by avian postembryonic growth plate chondrocytes.

We examined the in vitro effects of pituitary-derived chicken growth hormone (cGH), recombinant human insulin-like growth factor-I (rhIGF-I), recombinant human basic fibroblast growth factor (rhbFGF), and porcine transforming growth factor beta (pTGF-beta) on proliferation ([3H]thymidine uptake) and matrix proteoglycan synthesis (35SO4 incorporation) by chicken epiphyseal growth plate chondrocytes. Factorial experiments were used to study the effect of these substances in a serum-free culture system. Basic FGF had to be present in the culture medium for mitogenesis to take place. In the presence of this peptide, TGF-beta, TGF-beta + IGF-I, and newborn calf serum (NCS) stimulated mitogenesis. The mitogenic activity of NCS could be duplicated by adding platelet-derived growth factor (PDGF) to the culture medium. For matrix synthesis, IGF-I was the key factor, with the addition of TGF-beta, TGF-beta+bFGF, or serum producing further stimulation in matrix synthesis. Using this culturing system, homologous cGH did not stimulate cell proliferation or proteoglycan synthesis. The lack of stimulatory activity of cGH was consistent, regardless of the age of the birds from which the chondrocytes were isolated, the zone of the growth plate, or the level of cGH used. None of the growth factors used in this study or several other systemic hormones were found to be permissive factors for GH to be active. Either other factors must be present for a direct effect of GH on growth plate chondrocytes, or the avian species differ from their mammalian counterpart.

Animals↗
PubMed1977

Embryonic and postnatal growth of rat and mouse. V. Prenatal growth of organs and tissues, general principles: allometric growth, absence of growth, and the genetic regulation of the growth process.

(1) The investigation yielded several general growth principles, i.e., types of growth occurring rather frequently: (a) allometric growth, (b) a non-changing growth rate, persisting when the growth rate changes in the majority of tissues, (c) a growth rate equal to that of the whole embryo, (d) absence of growth and (e) jumps, i.e., changes in the volume or surface of organs completed within about half a day or less and probably due to changes in the cell volume or surface area; these histological changes tend to start simultaneously with the changes in growth rate. (2) Growth constants tend to have a value of about 2.0 in the prenatal period, as in the post-natal period. During development, however, their value increases slightly but significantly. (3) Further arguments are given for the mitosis-regulating model described in Part III. (4) The mitosis-regulating model combined with the general growth principles derived here and in earlier parts of this report constitute a comprehensive model for the genetiv regulation of the growth process.

Age Factors↗
PubMed1996

Growth factors and intrauterine growth retardation. I. Serum growth hormone, insulin-like growth factor (IGF)-I, IGF-II, and IGF binding protein 3 levels in normally grown and growth-retarded human fetuses during the second half of gestation.

The aim of this study was to relate human fetal growth retardation to specific hormone alterations. Serum levels of GH, IGF-I, IGF-II, and IGF binding protein (BP) 3 were measured during the second half of gestation after cordocentesis in 230 fetuses who were classified into normally grown (n = 166) and growth-retarded (n = 64) groups according to ante- and neonatal measurements. The normally grown group showed a progressive decline in serum GH levels toward term (r = -0.42, p = 0.0001), whereas serum IGF-I was increased (r = 0.55, p = 0.0001), as were serum IGF-II (r = 0.21, p = 0.008) and IGFBP3 levels (r = 0.19, p = 0.02), although less markedly. For all hormone levels, wide individual differences were found at any given age of gestation. The incidental presence of fetal malformations in either the normally grown group (n = 107 cases) or the growth-retarded group (n = 50 cases) had no apparent effect on these hormone levels as compared with members of the groups showing no fetal malformations (n = 73 cases). Comparison of the normally grown group with the growth-retarded group showed that serum IGF-I levels were significantly lower in the growth-retarded group (p = 0.001). No differences were found between the groups in serum GH, IGF-II, and IGFBP3 levels, although if data for the third trimester were taken alone, serum IGF-II levels were found to be lower in the growth-retarded group (p = 0.05). In conclusion, during the second half of gestation, fetal serum IGF-I levels may be influenced by nutritional factors controlling fetal growth. However, the wide individual differences in measurements make it a very poor biologic marker of intrauterine growth retardation.

Biomarkers↗
PubMed1993

Prediction of the growth response in children with various growth disorders treated with growth hormone: analyses of data from the Kabi Pharmacia International Growth Study. International Board of the Kabi Pharmacia International Growth Study.

Analyses to predict the growth response to recombinant human growth hormone (GH) in prepubertal children during the first year of treatment were performed on data from 472 patients with idiopathic GH deficiency (IGHD), 202 children with Turner's syndrome, 327 children with idiopathic short stature (ISS) and 135 children with intrauterine growth retardation (IUGR). In IGHD, 56% of the variability of the response could be predicted from a model based on six variables. These variables could be ranked in order of importance as follows: target height SDS minus height SDS, chronological age, frequency of GH injections, dose of GH, weight-for-height index, and birth weight SDS. When the model for IGHD was applied to Turner's syndrome, ISS and IUGR, there was a high degree of similarity between the predicted and achieved growth response in ISS and IUGR. However, an uneven distribution within the plot of Studentized residuals in ISS and IUGR suggested heterogeneity within these populations. Prediction of growth in Turner's syndrome was greatly exaggerated by the model for IGHD, suggesting a different pathogenesis as the basis of the growth disorder. Specific prediction models were therefore developed for Turner's syndrome, ISS and IUGR. In all three disorders, the dose of GH was found to be the most important predictor, suggesting that, in contrast to IGHD, first-year growth is governed less by the difference between height and the presumed genetically determined target height. Again, in contrast to IGHD, this suggests that catch-up phenomena are not involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1994

Epidermal growth factor, transforming growth factor alpha, transforming growth factor beta, acidic fibroblast growth factor, basic fibroblast growth factor, and interleukin-1 proteins in the cornea.

The purpose of this study was to determine whether epidermal growth factor (EGF), EGF receptor, transforming growth factor alpha (TGF-alpha), transforming growth factor beta (TGF-beta), acidic fibroblast growth factor (acidic-FGF), basic fibroblast growth factor (basic-FGF), and interleukin-1-alpha (IL-1-alpha) proteins were present in cultures of human corneal cells and/or in sections of human corneal tissue. Immunohistochemistry was performed on human corneal sections. Immunofluorescent cell staining was used to evaluate corneal epithelial, stromal fibroblast, and endothelial cells in primary culture. Basic-FGF production was evaluated in culture cells using immunoprecipitation. EGF, TGF-alpha, TGF-beta-1, and IL-1-alpha were detected by immunohistochemistry in cells in all three layers of the cornea. EGF receptor and acidic FGF were detected by immunohistochemistry in epithelial and endothelial cells, but not in stromal fibroblast cells. Differences in distribution of the growth factors were noted within individual layers of the cornea. EGF and basic-FGF proteins were detected in all three predominant cell types of the cornea using immunocytology. IL-1-alpha protein was detected by immunocytology in corneal epithelial and endothelial cells, but not stromal fibroblasts. Immunoprecipitation confirmed the production of basic-FGF in all three cell types. IL-1-alpha protein detection in the corneal stroma by immunohistology, but not by immunocytology in first passage stromal fibroblasts, suggests that IL-1-alpha may localize to the corneal stroma after production by corneal epithelial and/or endothelial cells.

Adult↗
PubMed1993

Synergistic action of angiotensin II, insulin-like growth factor-I, and transforming growth factor-beta on platelet-derived growth factor-BB, basic fibroblastic growth factor, and epidermal growth factor-induced DNA synthesis in vascular smooth muscle cells.

The effect of angiotensin II (AII), transforming growth factor-beta (TGF-beta), and insulin-like growth factor-I (IGF-I) on platelet-derived growth factor (PDGF)-BB-, basic fibroblastic growth factor (bFGF)-, and epidermal growth factor (EGF)-induced DNA synthesis in vascular smooth muscle cells (VSMCs) was investigated. TGF-beta, AII, IGF-I increased concentration-dependent cell protein. No increase in [3H]thymidine incorporation could be detected. TGF-beta, AII, and IGF-I enhanced PDGF-BB-, bFGF-, and EGF-induced DNA synthesis. Our results suggest that growth factors that possess a weak mitogenic effect on vascular smooth muscle cells such as TGF-beta, AII, and IGF-I may enhance the mitogenicity of PDGF-BB, bFGF, and EGF.

Angiotensin II↗
PubMed1993

Effect of timing of growth hormone administration on plasma growth-hormone-binding activity, insulin-like growth factor-I and growth in children with a subnormal spontaneous secretion of growth hormone.

Since normal pulsatile growth-hormone (GH) secretion displays a major and consistent surge during sleep, we studied the effect of timing of GH supplementation on plasma GH-binding protein activity (GH-BP), insulin-like growth factor-I (IGF-I) and growth. 34 prepubertal subjects (28 boys, 6 girls) aged 8-11 years, of short stature (< 2 SD for age), with a GH response to provocative test > 10 micrograms/l and a subnormal 24-hour GH secretion (< 3 micrograms/l), were randomly allocated to receive Bio-Tropin (recombinant GH, Bio-Technology, Israel) 0.81 IU/kg/week in 3 equally divided doses. GH was administered either at 8.00-10.00 h (M group), 14.00-16.00 h (AN group) or 19.00-21.00 h (NT group). Height velocity, IGF-I and GH-BP were determined prior to and after 6 and 12 months on GH therapy in the three groups. There was no significant difference between the three groups in the growth response, IGF-I and GH-BP increase, all of which increased significantly during GH therapy. Although GH levels after the injection decline to preinjection levels after 10 h, the changes induced by GH therapy, as reflected in IGF-I and GH-BP, last in the circulation long enough to prevent fluctuations in its action. The similarity of IGF-I and of GH-BP levels in the three treatment groups might explain the similar growth effects of the 3 protocols.

Carrier Proteins↗
PubMed1994

Effects of transforming growth factor-beta 1 and fibroblast growth factor on DNA synthesis in growth plate chondrocytes are enhanced by insulin-like growth factor-I.

The local tissue metabolism is controlled through the complex interaction between systemic and local growth factors. In recent years, an increasing number of autocrine or paracrine growth regulators have been identified in physeal cartilage. While these factors act to alter chondrocytes phenotypically and presumably are important mediators in the process of endochondral ossification, the manner in which they interact with the systemically regulated growth factor insulin-like growth factor-I is unknown. In the present study, the interactive effects of insulin-like growth factor-I with transforming growth factor-beta 1 or basic fibroblast growth factor were examined in short-term monolayer cultures of chick growth plate chondrocytes. [3H]thymidine incorporation was maximally stimulated 11-fold by fibroblast growth factor (10 ng/ml) and 3.5-fold by transforming growth factor-beta 1 following a 24-hour exposure in serum-containing cultures. The effects of transforming growth factor-beta 1 and fibroblast growth factor at both high and low concentrations were enhanced in a dose-dependent manner by insulin-like growth factor-I, with a 40-50% increase in DNA synthesis in the presence of 100 ng/ml of insulin-like growth factor-I. Since insulin-like growth factor-I increased [3H]thymidine incorporation after 48 hours (50% increase) but not after 24 hours of exposure, these observations represent a synergistic interaction. Total DNA in cultures treated for 5 days confirmed the modulating effect of insulin-like growth factor-I with transforming growth factor-beta 1 and fibroblast growth factor. The growth factors were further examined for their effects on markers of chondrocyte differentiation. While all three caused a dose-dependent inhibition of alkaline phosphatase activity, the effects of insulin-like growth factor-I were additive only to those of transforming growth factor-beta 1 and fibroblast growth factor. Similarly, insulin-like growth factor-I did not affect the sulfate incorporation stimulated by fibroblast growth factor or transforming growth factor-beta 1. Insulin-like growth factor-I had no effect on total protein synthesis after 24 hours and, although type-II collagen mRNA levels were stimulated, it had no effect on type-X collagen mRNA, as determined by quantitative in situ hybridization. Finally, insulin-like growth factor-I did not alter the dose-dependent stimulation of noncollagen protein synthesis and the inhibition of collagen synthesis caused by fibroblast growth factor and transforming growth factor-beta 1 in 24-hour cultures. Thus, the data suggest that insulin-like growth factor-I may have a role in augmenting the effects of other growth factors found in cartilage.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Keratinocyte growth inhibition by high-dose epidermal growth factor is mediated by transforming growth factor beta autoinduction: a negative feedback mechanism for keratinocyte growth.

The epidermal growth factor receptor and its ligands initiate a major signaling pathway that regulates keratinocyte growth in an autocrine manner. It is well known that high doses of epidermal growth factor receptor ligands inhibit keratinocyte growth. Recently, signal transducers and activators of transcription 1-dependent p21Waf1/Cip1 induction were reported to be involved in high-dose epidermal growth factor-dependent cell growth arrest in the A431 squamous cell carcinoma cell line; however, transfection of dominant-negative signal transducers and activators of transcription 1 adenovirus vector did not block epidermal growth factor-induced growth inhibition in normal human keratinocytes. As transforming growth factor beta is a potent inhibitor of keratinocyte proliferation, we hypothesized that transforming growth factor beta contributes to epidermal growth factor-mediated keratinocyte growth inhibition. Epidermal growth factor concentrations of 10 ng per ml enhanced transforming growth factor beta1 mRNA expression from 3 to 6 h poststimulation. Enzyme-linked immunosorbent assay analysis detected 150 pg per ml of transforming growth factor beta1 in the culture medium of keratinocytes incubated with 10 and 100 ng per ml epidermal growth factor, whereas 0.1 and 1.0 ng per ml epidermal growth factor slightly enhance transforming growth factor beta1 production. Epidermal growth factor (100 ng per ml) upregulated luciferase activity of p3TP-lux, which contains three tandem transforming growth factor beta-Smad signaling responsive elements, 6-fold compared with unstimulated cells. The epidermal growth factor-dependent induction of p3TP-lux luciferase activity was disrupted by transfection of the dominant negative form of transforming growth factor beta type I receptor adenovirus vector (AxdnALK5), which suggests that epidermal growth factor-induced transforming growth factor beta acts in an autocrine manner in keratinocytes. Moreover, transfection of AxdnALK5 completely blocked the growth inhibition induced by 100 ng per ml of epidermal growth factor in normal keratinocytes. These data demonstrate that an autocrine transforming growth factor beta1-ALK5 pathway is a negative feedback mechanism for epidermal growth factor-induced normal human keratinocyte growth.

Activin Receptors, Type I↗
PubMed1996

Growth factors and intrauterine growth retardation. II. Serum growth hormone, insulin-like growth factor (IGF) I, and IGF-binding protein 3 levels in children with intrauterine growth retardation compared with normal control subjects: prospective study from birth to two years of age. Study Group of IUGR.

The aim of this study was to describe serum GH, IGF-I, and IGF binding protein (BP) 3 levels at birth and during the first 2 y of life in intrauterine growth-retarded (IUGR) children and to correlate these hormonal values with auxologic parameters noted during this period to investigate their predictive value on the postnatal growth pattern. Three hundred and seventeen children were included at birth and studied for auxologic and biologic parameters at birth, 3 and 30 d, and 3, 6, 12, 18, and 24 mo of age. At birth, when analyzed according to gestational age, serum GH levels were increased (p = 0.0001) and serum IGF-I and IGFBP3 levels were decreased (p = 0.0001) in IUGR as compared with normal neonates. When two cohorts were established at birth as a function of the ponderal index (PI) (< or = or > 3rd percentile), serum IGF-I and IGFBP3 levels were found to be significantly reduced in the case of low PI. All parameters were within normal limits at 1 mo of age and remained normal thereafter. During the first 3 mo of life, a positive correlation was found between IGF-I increment and weight gain (r = 0.28, p = 0.002). None of the biologic parameters at birth were predictive either of later growth or of short stature at 2 y of age. In conclusion, low serum IGF-I and IGFBP3 levels at birth were related to fetal malnutrition and were not predictive parameters for later growth.

Body Height↗
PubMed1990

Growth response in the first year of growth hormone treatment in prepubertal children with organic growth hormone deficiency: a comparison with idiopathic growth hormone deficiency. The Executive Scientific Committee of the Kabi International Growth Study.

Patients in the Kabi International Growth Study (KIGS) up to 1st January 1990 who had organic growth hormone deficiency (OGHD) were identified. They accounted for 21% of all patients with growth hormone deficiency (GHD). Diagnostic categories within the OGHD group included septo-optic dysplasia, postnatal trauma, craniopharyngioma, other cranial tumours, and following acute leukaemia. Features at presentation and during the first year of hGH treatment were compared with those of children with idiopathic growth hormone deficiency (IGHD). Ninety prepubertal children with OGHD were selected for comparison of observed first-year height velocity (HV) with predicted values based on those observed in 257 children with IGHD. Those with septo-optic dysplasia, postnatal trauma and craniopharyngioma responded as predicted, whereas those with other cranial tumours appeared to grow less well than predicted. Glucocorticoid treatment did not affect response, but previous cranial or craniospinal irradiation was found to be associated with an observed HV which was significantly less than predicted.

Adolescent↗
PubMed1986

Induction and modulation of anchorage-independent growth by platelet-derived growth factor, fibroblast growth factor, and transforming growth factor-beta.

Transforming growth factors (TGFs) reversibly induce the anchorage-independent growth of nontransformed cells. TGF activity is often monitored by the growth of normal rat kidney (NRK) fibroblasts in soft agar, and it is known that more than one growth factor is involved in the regulation of their soft agar growth. To more clearly define the growth factors responsible for the soft agar growth of NRK cells, the effects of four growth factors were examined: platelet-derived growth factor (PDGF); TGF-beta; epidermal growth factor (EGF); and fibroblast growth factor (FGF). This study determined that PDGF induces the soft agar growth of NRK cells, in both plasma-supplemented medium and serum-free medium supplemented with FGF, and neither TGF-beta nor an EGF-related growth factor is required for this effect. It was also determined that FGF, which alone does not induce the soft agar growth of these cells, potentiates the responses of NRK cells to various combinations of PDGF, TGF-beta, and EGF. Interestingly, the effect of TGF-beta was found to depend on the growth factor composition of the medium. In the absence of EGF, TGF-beta partially inhibits the soft agar growth response of NRK cells to PDGF, whereas, in the presence of EGF, TGF-beta increases their response to PDGF. These findings indicate that at least four unrelated growth factors regulate the anchorage-independent growth of NRK cells. These findings have important implications for the use of NRK cells to assay TGFs.

Agar↗