摘要:

AbstractEpidermal growth factor (EGF) was administered by chronic subcutaneous or intracolonic infusion into normal adult rats to determine the effect on colonic growth. Subcutaneous infusion of 200μg EGF/kg/day for 7 days increased the cross-sectional mass and protein content of the muscularis and mucosal layers of the proximal colon, with the distal colon showing less response. In the mucosa, subcutaneous EGF induced proportional increments in the number of cells per crypt, and in the number of cells positively labelled for PCNA, while maintaining a normal crypt growth fraction. In contrast, an 8-fold higher dose of EGF administered intraluminally had no effect on colonic mucosal or muscularis growth. This lack of bioactivity was unlikely to reflect rapid luminal degradation as radiolabelled EGF remained stable in the colonic lumen for at least 4 h. The results demonstrate that the normal adult colon is responsive to subcutaneously delivered EGF, particularly the proximal colon, whereas EGF may not be active on the normal colon when presented from the luminal direction.

ISSN:0897-7194    

DOI:10.3109/08977199409000233

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractWe investigated whether development of pulmonary fibrosis following inhalational exposure of mice to silica (quartz) dust was accompanied by enhanced secretion of activity resembling epidermal growth factor (EGF). Mitogenic activity for pulmonary fibroblasts was assessed in bronchoalveolar lavage fluid (BALF) using a serum-free bioassay. Activity in BALF from mice exposed to nonfibrogenic titanium dioxide dust was comparable to that in BALF from normal animals. In contrast, mitogenic activity was significantly increased at 6 and 12 weeks after inhalation of silica particles, coinciding with the appearance of collagenised lesions in the lung. BALF from mice exposed to silica 6 weeks previously had significantly higher concentrations of growth factor(s) able to bind to EGF receptors on pulmonary fibroblasts. In parallel, macrophages within inflammatory lesions in the airspaces acquired immunoreactivity for EGF. The presence of an increased concentration of EGF-like growth factor(s) in BALF might constitute a marker of particle-induced pulmonary fibrosis.

ISSN:0897-7194    

DOI:10.3109/08977199409000234

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractTo develop a model for studies of liver growth control, we characterized cell cycle synchronization of liver-derived cells with sodium butyrate. Exposure of cultured HTC (rat hepatoma) cells to 5 mM butyrate arrested cell growth in a reversible manner. Flow cytometric analysis revealed that butyrate-treated HTC cells were restricted in G0/G1, as well as S/G2M phases. After release from butyrate arrest, HTC cells underwent synchronous cycles of DNA synthesis and transited through S phase. Inhibition of cell growth by butyrate was associated with a complex pattern of cell cycle regulated gene expression, including a decoupling of c-fosand c-jungene expression. Transcription of c-fos, as well as c-junincreased with butyrate arrest, whereas steady rate mRNA levels of c-junonly were increased, suggesting additional regulation of c-fos. In addition, butyrate-arrested cells exhibited a transcriptionally determined accumulation of H3 histone, C-Ha-rasand ornithine decarboxylase mRNAs, suggesting that cell cycle-related check points following the onset of S phase were modulated. An increase in c-mycmRNA levels in butyrate-arrested cells was post-transcriptionally regulated. After release from butyrate-arrest, the abundance of immediate early, as well as S phase regulated, gene expression changed coordinately with S phase cell transitions. Thus, exposure of HTC cells to butyrate modulates cell cycle regulated gene expression, inhibits cycling, and results in accumulation of cells in specific compartments. Synchronization of liver cells with butyrate should, therefore, provide a useful model for defining cell cycle-related events in response to various mitogenic stimuli.

ISSN:0897-7194    

DOI:10.3109/08977199409000235

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractThe activity of phosphatidylinositol (PI) 3-kinase was examined in murine bone marrow-derived macrophages (BMM) stimulated with the haematopoietic growth factors colony stimulating factor-1 (CSF-1) and granulocyte/macrophage-CSF (GM-CSF). PI 3-kinase was immunoprecipitated from cell lysates using anti-phosphotyrosine antibody or an antibody directed against the 85K subunit of PI 3-kinase, and the activity assayed by the phosphorylation of PI in the presence of [γ32P]-ATP. The results demonstrate that CSF-1 increases the activity of PI 3-kinase, as compared to the non-stimulated control, in murine macrophages. Maximum activity was seen after 10 min of stimulation with CSF-I at 3000–5000 U/ml. The dose-response of CSF-1 is consistent with other biochemical effects of CSF-1 seen in the BMM. GM-CSF also stimulated PI 3-kinase activity although to a lesser extent than CSF-1, correlating well with their degree of mitogenic activity on the BMM. Non-mitogenic macrophage activating agents, such as the phorbol myristate acetate, lipopolysaccharide, concanavalin A and formyl-methionyl-leucyl-phenylalanine, did not significantly increase the PI 3-kinase activity. Furthermore, CSF-1 failed to stimulate PI 3-kinase activity in resident peritoneal macrophages, a population of macrophages with poor proliferative capacity. These results suggest that the PI 3-kinase activity may be involved in the haemopoietic growth factor signalling pathways regulating macrophage growth.

ISSN:0897-7194    

DOI:10.3109/08977199409000236

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractWe have developed anin vitrobioassay for nerve growth factor (NGF) which offers several advantages over currently used alternatives. The assay uses the commercially available PC-12 cell line, and requires only 24 hr incubation with NGF. The cells do not require priming, and are dosed as they are originally seeded in serum-free medium in 96-well cell culture plates coated with collagen. Concentrations between one and 20 ng/ml NGF can be measured, and only standard cell culture equipment and a microplate reader are required.

ISSN:0897-7194    

DOI:10.3109/08977199409000237

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractWe report here that basic fibroblast growth factor (FGF-2), a potent mitogen for adrenocortical cells, stimulates the expression ofα2-macroglobulin by these cells at a transcriptional level and is synergistic with TGFβ1for this effect. This is supported by the following observations: (i) Treatment of adrenocortical cells by FGF-2 resulted in a time-dependent and dose-dependent increase ofα2M synthesis. (ii) FGF-2 did not modifyα2M secretion rate; (iii) The induction ofα2M synthesis by FGF-2 was not observed in the presence of the transcription inhibitor DRB; (iv) The amount ofα2M mRNA was increased by 2 to 3 fold under either FGF-2 or TGFβ1treatment; (v) Optimal doses of TGFβand FGF-2 synergis-tically increasedα2M synthesis. Sinceα2M is a growth factor-binding protein, its regulation by FGF-2 may represent an important feedback mechanism controlling the bioactivity of autocrine regulators (FGF-2, TFGβ) of adrenocortical functions.

ISSN:0897-7194    

DOI:10.3109/08977199409000238

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractWe have investigated changes in the synthesis and localization of insulin-like growth factor (1GF)-I and IGF binding proteins (IGFBPs) in thyroid tissues during the induction of goitre in iodine-deficient rats, and during the subsequent involution of the gland following goitrogen withdrawal. Goitre was induced in adult rats by acute (1 or 2 weeks) or chronic (4 or 10 weeks) administration of methimazole together with a low iodine diet. After twelve weeks the goitrogenic stimuli were removed and thyroids examined 4 weeks later. Circulating T4levels became undetectable within two weeks of goitrogen administration while thyroid weight had increased five-fold. The thyroids continued to increase in size up to 10 weeks, but at a slower growth rate. IGF-I mRNA, detected by ribonuclease protection assay, was present in the control rat thyroid and increased in abundance after both 1 and 2 weeks of goitrogen administration. Levels of IGF-I mRNA showed a relative decline with prolonged goitrogen administration, and following thyroid involution the hybridization signal was similar to that seen in control glands. Northern blot hybridization showed that IGFBP-2, -3 and -5 mRNAs were all present in growth-quiescent, control thyroids and those encoding IGFBP-2 and -3 were elevated in the goitrous glands and remained so as long as goitrogen was administered, thereafter declining during thyroid involution. IGF-I and IGFBP-2 and -3 mRNAs and synthesized peptides, detected byin situhybridization and immunohistochemistry respectively, were found to co-localize predominantly in follicular epithelial cells. IGFBP-5 mRNA abundance was unaltered during goitre formation, but was increased in the involuting thyroid. Both IGFBP-5 mRNA and peptide were localized to the parafollicular cells (C-cells) which were increased in number during involution. The results suggest that an increased expression of IGF-1 may contribute to early goitre formation, but that a relative increase in the abundance of IGFBP-2 and -3 may limit IGF availability at later times, and facilitate a slowing of thyroid growth rate. The discrete expression of IGFBP-5 by C-cells suggests that it could contribute indirectly to goitre formation or involution by acting in a paracrine fashion.

ISSN:0897-7194    

DOI:10.3109/08977199409000239

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractMany failures of vascular reconstructions are due to thrombosis and restenosis and are often attributed to inadequate endothelial regeneration at the site of endothelial denudation. Vascular permeability factor (VPF) is a naturally occurring growth factor responsible for vessel permeability and microvascular angiogenesis. Here, we show that VPF stimulated rabbit endothelial cell proliferationin vitroat concentrations 100 ng/ml. However, VPF had no effect on smooth muscle cell proliferation at these concentrations up to 500 ng/ml. When VPF was administered for 4 weeks (120μg, twice weekly, i.v.) following balloon angioplasty-induced endothelial denudation of rabbit carotid artery, there was a significant increase in thein vivoregeneration of endothelium compared to control (57.5±6.7 % vs. 38.3±1.9%, P>0.01). Moreover, 8 weeks of VPF administration resulted in 88.1±3.1% re-endothelialization compared to control (44.7±3.8%). Hence, VPF appears to be a specific mitogen for endothelial regeneration.

ISSN:0897-7194    

DOI:10.3109/08977199409000240

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor