摘要:

AbstractCollagen gene expression and proteoglycan synthesis are decreased in vitamin C-deficient guinea pigs losing weight and in fasted guinea pigs receiving ascorbate. Sera from such guinea pigs contain an insulin-like growth factor (IGF)-I-reversible inhibitor of collagen, proteoglycan and DNA synthesis and elevated levels of 29 and 35-kDa IGF binding proteins (IGFBPs). We now have identified the induced proteins as IGFBPs 1 and 2 and investigated their role as inhibitors. Guinea pig sera were treated with antibodies to IGFBPs 1 and 2 and antibody-IGFBP complexes were removed by passage through a Protein A-Sepharose column. Inhibitor content of fasted and scorbutic sera, and Protein A pass-through fractions derived from them, was assessed by their level of stimulation of DNA and collagen synthesis in 3T3 cells, compared to analogously treated normal guinea pig serum. Removal of IGFBP-1 from scorbutic serum reversed inhibition of collagen and DNA synthesis by more than half but removal of IGFBP-2 was less effective. Removal of both IGFBPs reversed inhibition almost completely. Similar results were obtained with fasted guinea pig serum. Conversely, purified rat IGFBPs 1 and 2 inhibited DNA and collagen synthesis in cells cultured in normal guinea pig serum or IGF-I-stimulated DNA synthesis, with IGFBP-1 being more potent. Thus, IGFBP-1 and, to a lesser extent IGFBP-2, cause inhibition of IGF-I action by sera from fasted and scorbutic guinea pigs and may inhibit collagen gene expression invivo.

ISSN:0897-7194    

DOI:10.3109/08977199409010989

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractThe effects of 7 days' s.c. infusion of 111-700μg/day IGF-1 on gut growth and absorptive function were examined in growing rats following removal of 70 or 80% of the jejuno-ileum, and compared with the responses to the analogues, LR3IGF-I and des(1-3)IGF-I, which bind poorly to IGF binding proteins. Administration of 278μg/day IGF-I, LR3IGF-I or des(1-3)IGF-I following 70% jejuno-ileal resection significantly attenuated malabsorption of fat and nitrogen. Responses in rats with 80% resection were less substantial, but a dose-responsive reduction in malabsorption was apparent with LR3IGF-I. Both IGF-I and LR3IGF-I were shown to increase body weight gain and food conversion efficiency in a dose-dependent manner following 80% jejuno-ileal resection. Total gut weight was increased by up to 21%, due predominantly to increased weight of the stomach and proximal small bowel, with the latter effect attributable at least in part to an increased bowel length. LR3IGF-l was more potent than IGF-l at stimulating body weight gain and food conversion efficiency, but its potency advantage on gut absorptive function and small intestinal re-growth was less marked. We conclude that administration of IGF-l peptides improves gastro-intestinal absorptive function following partial gut resection, most likely reflecting, at least in part, an increase in gut absorptive surface area.

ISSN:0897-7194    

DOI:10.3109/08977199409010990

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractEvidence fromin vitrostudies supports the concept that growth factors are involved in the function of endocrine organs. We studied the effects of target endocrine organs (thyroid, adrenals, and gonads) on levels of basic fibroblast growth factor (FGF-2) messenger ribonucleic acid (mRNA) in the anterior pituitary and the hypothalamus of male rats using RNase protection assays. Castration significantly reduced the levels of FGF-2 mRNA in the anterior pituitary, but not in the hypothalamus. This decrease was restored by testosterone administration. The regulation of pituitary FGF-2 mRNA involves a specific hormone, i.e. testosterone, since neither adrenalectomy nor chemical thyroidectomy affects the expression of the gene for FGF-2.

ISSN:0897-7194    

DOI:10.3109/08977199409010991

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractThe placenta undergoes extensive angiogenesis and cellular proliferation to establish adequate blood supply to the fetus. The aim of this study was to compare and contrast the immunolocalization of acidic and basic fibroblast growth factor (FGF) in both first trimester and term placenta and gestational decidua. Human choriocarcinoma cell line JEG-3 were employed as a model of cytotrophoblast and the effect of basic FGF on cell proliferation and phospholipase C and D activation investigated. Basic FGF-immunoreactivity (IR) was detected in or around cytotrophoblast cells and in extravillous trophoblast in first trimester placenta by immunohistochemistry using primary polyclonal rabbit antibodies. Identical staining patterns were produced by acidic FGF antibodies indicating colocalization of acidic FGF and basic FGF. At term, weaker and more diffuse staining was seen in the syncytiotrophoblast surrounding the placenta villi and strong staining was present in the smooth muscle cells of mid and large size placental vessels and in some endothelial cells. Endothelial cells and extravillous trophoblast stained strongly within the decidua at first trimester, whereas the glandular epithelium was weakly stained. Basic FGF induced [3H]thymidine incorporation in JEG-3 cells in a dose dependent manner and caused an increase in inosital phosphate accumulation in cells pre-labelled with myo-[3H]inosital at similar concentrations, suggesting a role of phospholipase C in JEG-3 cell proliferation. However, basic FGF failed to stimulate phospholipase D activity in cells pre-labelled with [3H]myristic acid. The detection of acid FGF and basic FGF on both maternal and fetal side of the placenta during early pregnancy suggests a role for FGF in angiogenesis, whereas localisation of the growth factor at term, when extensive angiogenesis has diminished, would indicate that FGF may be associated with more differentiated functions of the trophoblast. The nuclear localization of basic FGF in dividing but not non-dividing placental cells together with the effect of basic FGF on JEF-3 cells, strongly supports a role for basic FGF in cytotrophoblast proliferationin vivo.

ISSN:0897-7194    

DOI:10.3109/08977199409010992

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractThree fibroblast growth factors (FGFs), acidic FGF (FGF1), basic FGF (FGF2), and keratinocyte growth factor (FGF7) have been identified in prostate. to understand how FGFs regulate growth of the prostate, and to determine if regulation is altered in benign prostatic hyperplasia (BPH), the mitogenic potential of FGFs, receptor binding, and FGF-receptor (FGFR) gene expression of stromal (PS) and epithelial cells (PE) cultured from normal human prostate and BPH where determined. FGF1 and FGF2, but not FGF7, were mitogens for PS. FGF1 and FGF7 were potent mitogens for PE, but FGF2 was a weak mitogen for these cells. Both PS and PE exhibited high affinity binding (pM K) of iodinated-FGF2. The K was 4-fold and 12-fold higher for PS than for PE cultured from normal prostate and BPH, respectively. Northern analysis indicated that PS, but not PE, expressed FGFR typel (FGFR1) mRNA. The reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate FGFR type 2 (FGFR2) expression. The size of amplified DNA fragments, and nucleotide sequences, indicated that PS also expressed transcripts for the exon IIIc RNA splice variant of FGFR2. A RT-PCR product with the FGFR2 exon IIIb nucleotide sequence joined with the exon IIIc sequence was amplified with poly A+RNA from PE and primers spanning both exons. Thus, PE did not alternatively splice mRNA for FGFR2 exon IIIb and exon IIIc. No differences in the mitogenic potential of FGFs, receptor binding (K or number of sites), or FGFR gene expression were found in cells cultured from normal prostate and BPH.

ISSN:0897-7194    

DOI:10.3109/08977199409010993

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractThe secretion of transforming growth factor alpha (TGFa) and the expression of cell-surface receptors for epidermal growth factor (EGF) were measured in a series of human mammary cell lines. The amount of TGFa secreted by the cells did not correlate with the phenotype of the cells (epithelial or myoepithelial), the mechanism of immortalization of the cells (SV40 or spontaneous) or the source of the cells (normal mammary gland, benign hyperplastic lesion, malignant tumour). The level of expression of cell-surface receptors for EGF was markedly increased as a consequence of SV40-immortalization of mammary cells, but otherwise did not correlate with the phenotype of the cells or the source of the cells. Much of the increase was accounted for by the appearance of a large number of low-affinity receptors for EGF in the SV40-immortalized cells. It is suggested that one of the mechanisms whereby SV40-immortalization suppresses the senescence of primary cultures of human mammary epithelial cells involves increasing the level of expression of receptors for EGF. In contrast the level of secretion of TGFa by cells in culture is probably a consequence of the mechanisms of adaptation of each cell line to culture conditions, and does not reflect the level of secretion of TGFa by cells in vivo.

ISSN:0897-7194    

DOI:10.3109/08977199409010994

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractWe investigated thein vivodifferentiation potential of Y79 human retinoblastoma cells following pre-treatment with two novel neurotrophic agents: PEDF (human recombinant pigmented-epithelial derived factor) or IPM (interphotoreceptor matrix) wash. These agents were able to induce a significant degree of morphological differentiationin vitro. However, 48 days after subretinal transplantation of pre-treated cells, massive tumor formation was apparent. In contrast, Y79 cells pre-treated with retinoic acid/sodium butyrate, which attain a lesser degree of morphological differentiation, did not produce tumors over a 30 to 60 day-survival time (del Cerro et al.,Brain Research, 12–22, 1992). We conclude that for PEDF and IPM, the degree ofin vitrodifferentiation and the degree of mitotic arrest are independent features.

ISSN:0897-7194    

DOI:10.3109/08977199409010995

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractThe survival of tissues in the presence of arterial occlusion is critically dependent on the development of collateral blood vessels. Identification of the biochemical mediators and their mechanism of action is fundamental to an understanding of the evolution of the collateral circulation. The ability of PDGF-BB to promote this was evaluated in an animal model of hind limb ischaemia.In order to obtain significant quantities of this mitogen for use in our animal model, human recombinant PDGF-BB was expressed in a Chinese Hamster Ovary (CHO) cell line. The transfected CHO cells produced 544μg/l of PDGF-BB in serum free medium (SFM). The 30 kDa form of PDGF-BB was purified to homogeneity as judged by silver staining and amino-acid sequencing. Purified PDGF-BB was shown to be bioactive by a cell proliferation assay. The exogenous administration of PDGF-BB enhanced the recovery of blood flow after acute arterial occlusion. The results suggest that PDGF-BB may have therapeutic value in promoting collateral development following arterial occlusion.

ISSN:0897-7194    

DOI:10.3109/08977199409010996

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor