Micrograms Of Epidermal Growth Factor Research Articles

Epidermal growth factor enhances spontaneous sleep in rabbits.

Several growth factors are implicated in sleep regulation. Epidermal growth factor (EGF) is found in the brain, and it influences the production of several sleep-promoting substances. We determined, therefore, whether administration of exogenous EGF affected spontaneous sleep in rabbits. Twenty-five rabbits were implanted with electroencephalographic electrodes, a brain thermistor, and an intracerebroventricular guide cannula. Three doses of EGF (0.5, 5, and 25 microg) were used. The animals were injected intracerebroventricularly with saline as control and one dose of EGF on 2 separate days. Five and twenty-five micrograms of EGF enhanced non-rapid eye movement sleep and increased brain temperature. The 25-microg dose of EGF also inhibited rapid eye movement sleep across the 23-h postinjection recording period. Results are consistent with the hypothesis that EGF, like other growth factors, could be involved in sleep regulation.

The influence of epidermal growth factor on cat corneal endothelial wound healing

Using standardized freeze wounds in cat corneas, we tested the efficacy of human recombinant Epidermal Growth Factor (EGF) to promote endothelial healing when solubilized in either phosphate buffered saline (PBS), 1% methylcellulose (MC), or sodium hyaluronate (NaHA), in final intraocular doses ranging from 2 micrograms to 100 micrograms of EGF. After 6 or 7 days' healing, animals were humanely sacrificed and corneal tissues were fixed and stained for light microscopy and computation of remaining wound areas. EGF in NaHA in final intraocular doses of 2 and 10 micrograms prompted significantly more complete healing of transcorneal freeze wounds to endothelium compared with endothelium of eyes treated with NaHA control solution alone. EGF in PBS or in MC in doses ranging from 2-100 micrograms/eye did not promote more complete wound healing than that seen in eyes treated with their respective vehicle solutions alone. All vehicle solutions were associated with similar degrees of wound healing, implying that they have no intrinsic healing properties.

Effects of X Irradiation on Angiogenesis

We have evaluated the effect of X irradiation on the mesenchymal tissue growth (blood capillaries and stromal cells) in an angiogenesis system in the mouse. This was accomplished by implanting a polyvinyl alcohol sponge disc in the subcutis of the thorax, and quantifying the extent of growth reduction of capillaries and stromal cells following graded doses of X rays. The sponge disc contained a centrally located pellet impregnated with 20 micrograms of epidermal growth factor and coated with a thin film of slow-releasing compound. Total growth of vessels and fibroblasts was determined by morphometric analysis of histologic sections. The incorporation of [3H]TdR was measured during a 24-h period. A dose-response relationship was observed when X irradiation was given on Day 11 after implantation, with the disc removed on Day 20. A single dose of 15 Gy reduced both the rate of incorporation of [3H]TdR and the total growth area. These and previous observations point to endothelial cells as important targets of ionizing radiation in the stroma, especially during the period of active proliferation of these cells, induced by growth factors.

Epidermal Growth Factor (EGF) Receptors in Human Chorionic Gonadotropin-Producing Tumor: Transplantation in Nude Mice and the Effect of EGF on Tumor Growth

We examined the presence and characteristics of epidermal growth factor (EGF) receptors in hCG producing tumors (CC-2-JCK) transplanted in female nude mice. We also examined the in vivo effects of EGF on tumor growth. Specific receptors with apparent dissociation constants of 3.89 x 10(-10) and 1.0 x 10(-9) M and binding capacities of 5.96 x 10(-10) and 1.52 x 10(-9) M/mg protein for EGF have been identified in the hCG-producing tumor. [125I]EGF binding to the tumor tissues was time, temperature, and tissue weight dependent and specific. EGF and transforming growth factor-alpha (TGF alpha) competed for [125I]EGF binding, with 50% of the bound [125I]EGF displaced by approximately 0.52 nM EGF and 3.10 nM TGF alpha. TGF beta competed for [125I]EGF binding slightly. Five micrograms of EGF caused an increase in the rate of tumor growth, while 50 micrograms EGF strongly inhibited tumor growth. The concentration of [125I]EGF binding in the tumor treated with low doses of EGF was high, and that in the tumor treated with high doses of EGF was low. These changes in EGF binding were attributable to the changes in the number of high affinity EGF receptors with no significant alteration in binding affinity. In conclusion, the existence of high concentrations of EGF receptors with high affinity and specificity to EGF was demonstrated in an hCG-producing tumor transplanted in nude mice and appeared to be correlated with tumor growth.

Epidermal growth factor increases collagen production in granulation tissue by stimulation of fibroblast proliferation and not by activation of procollagen genes.

The effects of epidermal growth factor (EGF) on granulation-tissue formation and collagen-gene expression were studied in experimental sponge-induced granulomas in rats. After daily administration of 5 micrograms of EGF into the sponge, total RNA was extracted from the ingrown granulation tissue at days 4 and 7 and analysed by Northern hybridization for the contents of mRNAs for types I and III procollagens. EGF treatment increased procollagen mRNA, particularly at day 4. To determine whether this elevation was due to increased proliferation of collagen-producing fibroblasts or to activation of collagen-gene expression in these cells, fibroblast cultures were started from granulation tissue and treated with EGF. These experiments confirmed that EGF is a potent mitogen for granuloma fibroblasts in a dose-dependent manner. The effect of EGF treatment on radioactive hydroxyproline production in cultured cells was inhibitory. The decreased rate of collagen synthesis was also indicated by decreased amounts of procollagen mRNAs. The results suggest that the stimulation of wound healing and collagen production by EGF is due to increased fibroblast proliferation, and not to increased expression of type I and III procollagen genes.

Stimulation of wound healing by epidermal growth factor. A dose-dependent effect.

This work was undertaken to study the effects of various doses of locally applied epidermal growth factor (EGF) on developing granulation tissue in rats. Cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the test groups, the implants were injected daily with a solution containing 0.2, 1, or 5 micrograms of EGF in 0.1% albumin while the implants of the control group were treated correspondingly with the carrier solution only. Analyses of granulation tissue in the sponge cylinders were carried out 7 days after implantation. A stimulatory, dose-dependent effect of EGF on granulation tissue formation was observed: cellularity increased, as evidenced by the elevated amounts of nucleic acids, and accumulation of collagen and glycosaminoglycans was enhanced.

Sustained release of epidermal growth factor accelerates wound repair.

Epidermal growth factor (EGF) is a potent mitogen in vitro, but its biological role is less clear. The vulnerary effects of EGF were evaluated in a model of wound repair, the polyvinyl alcohol sponge implanted subcutaneously in rats. EGF was purified to homogeneity by reverse-phase HPLC and quantified by receptor binding assay and amino acid analysis. Preliminary data showed moderate promotion of granulation tissue formation by daily injections of 10 micrograms of EGF. To test the hypothesis that long-term exposure to EGF is required for complete cellular response, the factor was incorporated into pellets releasing 10 or 20 micrograms of biologically active EGF per day, and the pellets were embedded within the sponges. Slow release of EGF caused a dramatic increase in the extent and organization of the granulation tissue at day 7, a doubling in the DNA content, and 33% increases in protein content and wet weight, as compared with placebo controls. Although collagen content was also increased by almost 50%, the relative rate of collagen synthesis remained the same, suggesting that the morphological and biochemical increase in collagen resulted from increased numbers of fibroblasts rather than a specific stimulation of collagen synthesis. These results indicate that the local sustained presence of EGF accelerates the process of wound repair, specifically neovascularization, organization by fibroblasts, and accumulation of collagen.