Modulation of epidermal growth factor receptors on 3T3 cells by platelet-derived growth factor

Platelet-derived growth factor does not compete with epidermal growth factor (EGF) for binding to EGF receptors on the murine 3T3 cell surface, but it modulates EGF receptors in two ways: (i) it induces a transient down regulation of EGF receptors and (ii) it inhibits EGF-induced down regulation of EGF receptors. These data suggest a common cellular internalization mechanism for the receptors for both hormones.     

Nerve growth factor: stimulation of regenerative growth of central noradrenergic neurons

The growth of new axonal sprouts was studied from transected, ascending noradrenergic axons into transplants of iris tissue in the caudal hypothalamus of the rat. A single intraventricular injection of nerve growth factor, given at the time of axonal damage, resulted in an increased formation and growth of new noradrenaline sprouts 7 days later. The effect seemed to be proportional to the administered dose of nerve growth factor.     

Nerve growth factor of very high yield and specific activity

Nerve growth factor has been isolated from submaxillary glands of mnature male mice at specific activities about a million times, and in yields of biological activity ten million times, greater than best previous results. The major improvement in the isolation is related to the separation of a highly active tosylarginine methyl esterase present in cruder preparations. The new nerve growth factor may be an entity different from the older one, although no gross differences in the qualitative aspects of their actions are apparent on superficial examination of chick ganglia influenced by them. The neurites which develop from a ganglion in the presence of nerve growth factor are of nearly equal length. The amount of nerve growth factor determines the number of neurites but not the extent of individual development. The amount of the new nerve growth factor which evokes the appearance of a hundred neurites from a single ganglion appears to be about ten molecules. Since each neurite seems to arise from a different neuron each molecule of nerve growth factor must affect several cells. This result can be rationalized by a catalytic mechanism or by indirect action of nerve growth factor through a hypothetical cell which produces a neurite evocator on contact with the molecule of nerve growth factor.     

Vascular endothelial growth factor is a secreted angiogenic mitogen

Vascular endothelial growth factor (VEGF) was purified from media conditioned by bovine pituitary folliculostellate cells (FC). VEGF is a heparin-binding growth factor specific for vascular endothelial cells that is able to induce angiogenesis in vivo. Complementary DNA clones for bovine and human VEGF were isolated from cDNA libraries prepared from FC and HL60 leukemia cells, respectively. These cDNAs encode hydrophilic proteins with sequences related to those of the A and B chains of platelet-derived growth factor. DNA sequencing suggests the existence of several molecular species of VEGF. VEGFs are secreted proteins, in contrast to other endothelial cell mitogens such as acidic or basic fibroblast growth factors and platelet-derived endothelial cell growth factor. Human 293 cells transfected with an expression vector containing a bovine or human VEGF cDNA insert secrete an endothelial cell mitogen that behaves like native VEGF.     

Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor

Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) are structurally related peptides. Purified human TGF-alpha produced in Escherichia coli and pure natural mouse EGF were compared for their ability to bind to target cells in vitro and to promote angiogenesis in the hamster cheek pouch bioassay. Both polypeptides were found to bind in vitro to several target cells, including endothelial cells, and to stimulate their DNA synthesis in an equipotent fashion. In vivo, however, TGF-alpha was more potent than EGF in promoting angiogenesis and, because TGF-alpha is known to be secreted by a variety of human tumors, it is suggested that this growth factor may contribute to tumor-induced angiogenesis.     

Epithelial wound healing enhanced by transforming growth factor-alpha and vaccinia growth factor

Epidermal regeneration following middermal injuries to skin requires both proliferation and migration of keratinocytes. Epidermal growth factor (EGF) stimulates the proliferation of keratinocytes in culture, and topical administration of EGF accelerates epidermal regeneration of partial thickness burns or split-thickness incisions in vivo. Transforming growth factor-alpha (TGF-alpha) and vaccinia growth factor (VGF) have substantial sequence homology with EGF, and all appear to bind to the same receptor protein. Whether TGF-alpha or VGF can affect epidermal wound healing in vivo is not known. The present studies show that topical administration of TGF-alpha or VGF in antibiotic cream to partial thickness burns (second degree) accelerated epidermal regeneration in comparison with untreated or vehicle-treated burns. Low levels of both TGF-alpha and VGF (0.1 microgram per milliliter) appeared to be more effective than EGF in stimulating epidermal regeneration. Regenerated epithelium from burns treated with TGF-alpha or VGF appeared normal histologically. This finding suggests that topical application of selected growth factors may be useful in accelerating healing of partial thickness injuries.     

Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor

A tumor-derived growth factor that stimulates the proliferation of capillary endothelial cells has a very strong affinity for heparin. This heparin affinity makes it possible to purify the growth factor to a single-band preparation in a rapid two-step procedure. The purified growth factor is a cationic polypeptide, has a molecular weight of about 18,000, and stimulates capillary endothelial cell proliferation at a concentration of about 1 nanogram per milliliter.     

Overexpression of transforming growth factor alpha in psoriatic epidermis

Transforming growth factor alpha (TGF-alpha) is produced by and required for the growth of epithelial cells and is angiogenic in vivo. Since epidermal hyperplasia and angiogenesis are hallmarks of psoriasis, TGF-alpha gene expression was analyzed in epidermal biopsies of normal and psoriatic skin. TGF-alpha messenger RNA and protein are much more abundant in lesional psoriatic epidermis than in normal-appearing skin of psoriatic patients or in normal epidermis. In contrast, messenger RNA levels of transforming growth factor beta 1 (TGF-beta 1), which inhibits epithelial cell growth, are not significantly different in normal, uninvolved, and lesional psoriatic epidermis. Thus, psoriatic epidermal hyperplasia may involve increased expression of a keratinocyte mitogen (TGF-alpha) rather than deficient expression of a growth inhibitor (TGF-beta 1).     

Potent interaction between glucocorticoids and growth hormone-releasing factor in vivo

Administration of dexamethasone significantly enhanced the pituitary growth hormone response to growth hormone-releasing factor in intact as well as adrenalectomized rats. Thus the inhibitory effects of glucocorticosteroids on somatic growth which involve an interaction of these steroids and growth hormone at a peripheral level may also involve a modification of pathways within the central nervous system that regulate normal growth hormone secretion.     

Physiological effects of transforming growth factor in the newborn mouse

Transforming growth factor-type alpha accelerated incisor eruption and eyelid opening in the newborn mouse and also retarded the growth rates of hair and body weight when administered in high dosage (0.7 to 4 micrograms per gram of body weight). The results of whole animal studies indicate that transforming growth factor-type alpha and epidermal growth factor do not differ significantly in these effects and suggest that transforming growth factor-type alpha may be important in immature animals.     

Nerve growth factor attenuates neurotoxic effects of taxol on spinal cord-ganglion explants from fetal mice

Most neurons in organotypic cultures of dorsal root ganglia from 13-day-old fetal mice require high concentrations of nerve growth factor for survival during the first week after explanation. These nerve growth factor-enhanced sensory neurons mature and innervate the dorsal regions of attached spinal cord tissue even after the removal of exogenous growth factor after 4 days. In cultures exposed for 4 days to nerve growth factor and taxol (a plant alkaloid that promotes the assembly of microtubules) and returned to medium without growth factor, greater than 95 percent of the ganglionic neurons degenerated and the spinal cord tissues were reduced almost to monolayers. In contrast, when the recovery medium was supplemented with nerve growth factor, the ganglionic neurons and dorsal (but not ventral) cord tissue survived remarkably well. Dorsal cord neurons do not normally require an input from dorsal root ganglia for long-term maintenance in vitro, but during and after taxol exposure they become dependent for survival and recovery on the presence of neurite projections from nerve growth-factor-enhanced dorsal root ganglia.     

Choline acetyltransferase activity in striatum of neonatal rats increased by nerve growth factor

Some neurodegenerative disorders may be caused by abnormal synthesis or utilization of trophic molecules required to support neuronal survival. A test of this hypothesis requires that trophic agents specific for the affected neurons be identified. Cholinergic neurons in the corpus striatum of neonatal rats were found to respond to intracerebroventricular administration of nerve growth factor with prominent, dose-dependent, selective increases in choline acetyltransferase activity. Cholinergic neurons in the basal forebrain also respond to nerve growth factor in this way. These actions of nerve growth factor may indicate its involvement in the normal function of forebrain cholinergic neurons as well as in neurodegenerative disorders involving such cells.     

Construction of a novel oncogene based on synthetic sequences encoding epidermal growth factor

The autocrine model postulates that constitutive release of a mitogenic growth factor can lead to uncontrolled proliferation and cell transformation. A synthetic polynucleotide encoding epidermal growth factor conferred a tumorigenic phenotype on cells. These cells were transformed through the action of an autocrine circuit having an extracellular component.     

农业结构调整对农业全要素生产率增长的影响效应

[目的]在边际报酬递减规律与资源环境的共同约束下,依靠要素投入推动农业增长不可持续,因此,不断提高农业全要素生产率（TFP）对中国农业可持续增长尤其重要。[方法]采用乘积完备（multiplicatively complete）的Hicks-Moorsteen全要素生产率指数,将中国农业全要素生产率增长彻底分解为技术进步、技术效率变化、规模效率变化和混合效率变化,农业结构调整通过改变混合效率,进而影响农业全要素生产率增长。[结果]从时间维度上看,仅1992-1997年混合效率变化为农业全要素生产率增长贡献了0.5个百分点,即该时期农业结构调整促进了农业全要素生产率增长。从地区维度上看,仅东部地区混合效率变化为东部地区农业全要素生产率增长贡献了0.4个百分点,即东部地区农业结构调整推动了东部地区农业全要素生产率增长。中国农业全要素生产率增长主要来自技术进步,农业结构调整对农业全要素生产率增长的影响效应在时空上存在较大差异。[结论]农业结构应根据市场需求、资源禀赋和比较优势进行调整,才能提高混合效率,进而推动农业全要素生产率增长。     

Nerve growth factor: relationship to the cyclic AMP system of sensory ganglia

Nerve growth factor and N(6),O(2)' dibutyryl adenosine 3',5'-monophosphate both stimulate neurite elongation by explanted ganglia. However, the addition of nerve growth factor does not lead to increased amounts of adenosine 3',5'-monophosphate in intact ganglia, nor does it stimulate adenylate cyclase activity in broken ganglia cells.     

Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation

Closely related signals often lead to very different cellular outcomes. We found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF). We used mass spectrometry-based proteomics to comprehensively compare proteins that were tyrosine phosphorylated in response to EGF and PDGF and their associated partners. More than 90% of these signaling proteins were used by both ligands, whereas the phosphatidylinositol 3-kinase (PI3K) pathway was exclusively activated by PDGF, implicating it as a possible control point. Indeed, chemical inhibition of PI3K in PDGF-stimulated cells removed the differential effect of the two growth factors, bestowing full differentiation effect onto PDGF. Thus, quantitative proteomics can directly compare entire signaling networks and discover critical differences capable of changing cell fate.     

A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF.

Macrophage-like U-937 cells secrete a 22-kilodalton heparin-binding growth factor that is mitogenic for BALB-3T3 fibroblasts and smooth muscle cells, but not endothelial cells. The amino acid sequence predicted from complementary DNA clones indicates that the mitogen is a new member of the epidermal growth factor (EGF) family. This heparin-binding EGF-like growth factor (HB-EGF) binds to EGF receptors on A-431 epidermoid carcinoma cells and smooth muscle cells, but is a far more potent mitogen for smooth muscle cells than is EGF. HB-EGF is also expressed in cultured human macrophages and may be involved in macrophage-mediated cellular proliferation.     

Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor

Purified growth inhibitor from BSC-1 cells and type beta transforming growth factor from human platelets are shown to have nearly identical biological activity and to compete for binding to the same cell membrane receptor. These findings suggest that the growth inhibitor and the type beta transforming growth factor are similar molecules. The data also show that the same purified polypeptide can either stimulate or inhibit cell proliferation depending on the experimental conditions.     

Nerve growth factor treatment after brain injury prevents neuronal death

Cholinergic neuronal degeneration after axotomy has been proposed to be due to the loss of a retrogradely transported neurotrophic factor, possibly nerve growth factor (NGF). To test this hypothesis, NGF was continuously infused into the lateral ventricles of adult rats that had received bilateral lesions of all cholinergic axons projecting from the medial septum to the dorsal hippocampus. After 2 weeks of NGF treatment, identification of cholinergic neurons by the presence of the biosynthetic enzyme choline acetyltransferase revealed a dramatic increase (350%) in the survival of the axotomized septal cholinergic neurons. Thus, NGF or an NGF-like molecule can act as a neurotrophic factor for these neurons.