• Radiation Oncology Journal
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• v.20 no.3
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• pp.253-263
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• 2002

Purpose : In order to understand in vivo radiation damage modifying of bFGF on jejunal mucosa, bone marrow and the effect of bFGF on the growth of transplanted mouse sarcoma 180 tumor in mice. Materials and Methods : Mice were treated with $6\;{\mu}g$ of bFGF at 24 hours and 4 hours before exposing to 600 cGy, 800 cGy and 1,000 cGy total body irradiation (TBI), and then exposed to 3,000 cGy local radiation therapy on the tumor bearing thigh. Survival and tumor growth curve were plotted in radiation alone group and combined group of bFGF and irradiation (RT). Histologic examination was performed in another experimental group. Experimental groups consisted of normal control, tumor control, RT (radiation therapy) alone, $6\;{\mu}g$ bFGF alone, combined group of $3\;{\mu}g$ bFGF and irradiation (RT), combined group of $6\;{\mu}g$ bFGF and irradiation (RT). Histologic examination was peformed with H-E staining in marrow, jejunal mucosa, lung and sarcoma 180 bearing tumor. Radiation induced apoptosis was determined in each group with the DNA terminal transferase nick-end labeling method ($ApopTag^{\circledR}$ S7100-kit, Intergen Co.) Results : The results were as follows 1) $6\;{\mu}g$ bFGF given before TBI significantly improved the survival of lethally irradiated mice. bFGF would protect against lethal bone marrow syndrome. 2) $6\;{\mu}g$ bFGF treated group showed a significant higher crypt depth and microvilli length than RT alone group (p<0.05). 3) The bone marrow of bFGF treated group showed less hypocellularity than radiation alone group on day 7 and 14 after TBI (p<0.05), and this protective effect was more evident in $6\;{\mu}g$ bFGF treated group than that of $3\;{\mu}g$ bFGF treated group. 4) bFGF protected against early radiation induced apoptosis in intestinal crypt cell but might have had no antiapoptotic effect in bone marrow stem cell and pulmonary endothelial cells. 5) There was no significant differences in tumor growth rate between tumor control and bFGF alone groups (p>0.05). 6) There were no significant differences in histopathologic findings of lung and mouse sarcoma 180 tumor between radiation alone group and bFGF treated group. Conclusions : Our results suggest that bFGF protects small bowel and bone marrow from acute radiation damage without promoting the inoculated tumor growth in C3H mice. Improved recovery of early responding normal tissue and reduced number of radiation induced apoptosis may be possible mechanism of radioprotective effect of bFGF.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.14-21
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• 1999

The immunogenicity of the recombinant human basic fibroblast growth factor (rh-bFGF) was investigated by tests for active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and guinea pig maximization test (GPMT) in mice or guinea pigs. Guinea pigs were sensitized with rh-bFGF ($100-1000\;\mu\textrm{g}/kg$) or rh-bFGF-CFA mixture ($1000\;\mu\textrm{g}/kg$). All animals sensitized with rh-bFGF alone or mixture with CFA showed symptoms of anaphylactic shock. IgE antibodies to rh-bFGF were detected in sera obtained from rh-bFGF and rh-bFGF-Alum ($1000\;\mu\textrm{g}/kg$) sensitized mice, indicating that rh-bFGF has immunogenicity eliciting potential. IgG and/or IgM antibodies to rh-bFGF were also detected in all the sera obtained from sensitized mice by PHA. In the GPMT for delayed type skin reaction, no skin reaction was observed in sensitized guinea pigs after intradermal injection and dermal application of 0.01% rh- bFGF. However, these positive reactions were consistent with the results of another rh-bFGF, showing that rh- bFGF is a heterogenous protein to rodents. Considering the fact that rh-bFGF is a genuine human protein of which structure is identical to the endogenous human bFGF, it is thought that rh-bFGF is rarely associated with immunological problems in clinical use.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.268-276
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• 2017

Background: UV-B-exposed keratinocytes secrete various paracrine factors. Among these factors, basic fibroblast growth factor (bFGF) stimulates the proliferation of melanocytes. Ginsenosides, the major active compounds of ginseng, are known to have broad pharmacological effects. In this study, we examined the antiproliferative effects of ginsenosides on bFGF-induced melanocyte proliferation. Methods: We investigated the inhibitory effects of Korean Red Ginseng and ginsenosides from Panax ginseng on bFGF-induced proliferation of melan-a melanocytes. Results: When melan-a melanocytes were treated with UV-B-irradiated SP-1 keratinocytes media, cell proliferation increased. This increased proliferation of melanocytes decreased with a neutralizing anti-bFGF antibody. To elucidate the effects of ginsenosides on melanocyte proliferation induced by bFGF, we tested 15 types of ginsenoside compounds. Among them, Rh3, Rh1, F1, and CK demonstrated antiproliferative effects on bFGF-induced melanocyte proliferation after 72 h of treatment. bFGF stimulated cell proliferation via extracellular signal-regulated kinase (ERK) activation in various cell types. Western blot analysis found bFGF-induced ERK phosphorylation in melan-a. Treatment with Rh3 inhibited bFGF-induced maximum ERK phosphorylation and F1-delayed maximum ERK phosphorylation, whereas Rh1 and CK had no detectable effects. In addition, cotreatment with Rh3 and F1 significantly suppressed bFGF-induced ERK phosphorylation. Western blot analysis found that bFGF increased microphthalmia-associated transcription factor (MITF) protein levels in melan-a. Treatment with Rh3 or F1 had no detectable effects, whereas cotreatment with Rh3 and F1 inhibited bFGF-induced MITF expression levels more strongly than a single treatment. Conclusion: In summary, we found that ginsenosides Rh3 and F1 have a synergistic antiproliferative effect on bFGF-induced melan-a melanocyte proliferation via the inhibition of ERK-mediated upregulation of MITF.

• Journal of Life Science
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• v.14 no.3
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• pp.375-384
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• 2004

Fibroblast growth factors (FGFs) are known to induce multiple functions in early development, including mesoderm formation, gastrulation movement and antero-posterior patterning. The induction of mesoderm from Xenopus presumptive ectoderm and the combination effect on inducing organs of bFGF(basic FGF) and HGF (Hepatocyte Growth Factor) were studied. Explants were cultured in the combined solution for 3 days to normal embryo arrive at St. 43. These effects on combined dose were examined by histological experiment and by immunohistochemical method. The concentrations of growth factors were tested in 0, 0.5, 1, 10 and also tested in 50 ng/ml of bFGF, and 0, 1, 10, 50 and 100ng/ml of HGF respectively. The synergistic effects were seen in the combined-dose of bFGF and HGF rather than in single dose. Various organs were differentiated and highest inducing effects were seen at the combined concentration of 1 ng/ml of bFGF and 10ng/ml of HGF, and at the concentration 10ng/ml of bFGF and 1 ng/ml of HGF. The bFGF induces various organs from cultured animal cap explants and the effects are time and dose-dependent. HGF is also a potent mitogen for renal tubular cells and for mature hepatocytes in primary culture. Eyes were developed in high percentage at the combined concentration of 1 and 10ng/ml of bFGF, and 1 and 10 ng/ml of HGF. From the induced eye and normal embryonic eye, RPE65 was commonly detected by monoclonal antibodies 40All and 25F5 and the localization of RPE65 was seen by AP reaction.

• Journal of the korean academy of Pediatric Dentistry
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• v.27 no.2
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• pp.300-308
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• 2000

The Fibroblast growth factors(FGFs) plays an important role in the control of osteogenesis during skeletal development. Especially, FGF-2 is a potent mesodermal inducer during embryogenesis and FGF receptors (FGFRs) messages are strongly expressed in developing bones. In this study, we investigated the effect of bFGF on osteopontin(OPN) gene expression in ST-2 cells and tried to elucidate the mechanism of its stimulatory effects. The obtain results were as follows; The treatment of bFGF(1ng/ml) upregulates OPN, fibronectin mRNA levels and downregulates type I collagen mRNA levels. But, there was no remarkable difference in alkaline phosphatase mRNA levels between two groups. The OPN gene expression increased in a dose-dependent manner up to 10ng/ml and OPN gene began to occur at around 3h with continuous increase up to 24h then decreased to basal level at 48h. 30 minutues pretreatment with cycloheximide (500ng/ml), a protein synthesis inhibitor, prior to addition bFGF resulted in blocking bFGF induced OPN expression. These results suggest that bFGF increased the level of OPN mRNA in a dose and time-dependent manner via the synthesis of certain transcriptional regulatory proteins.

• Archives of Plastic Surgery
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• v.38 no.5
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• pp.567-575
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• 2011

Purpose: Acellular human dermis is very useful implant for use in plastic and reconstructive surgery. However, the volume of acellular human dermis graft is known to decrease for a long time. Basic fibroblast growth factor (bFGF) is a polypeptide that enhances the collagen synthesis and angiogenesis. In the current study we examined whether bFGF could improve the survival of acellular human dermis ($SureDerm^{(R)}$) by increasing angiogenesis of the graft. Methods: Forty rats were divided into two groups (control and bFGF). A 2-mm thick piece of $SureDerm^{(R)}$ was cut into smaller pieces that were $15{\times}5$ mm in size. Two subcutaneous pockets were made on the back of each rat. Grafts sprayed with bFGF were implanted in the bFGF group and injected with bFGF after transplantation every 3 days for 2 weeks. In the control group, the grafts were treated with phosphate-buffered saline (PBS) instead of bFGF. Four days, and 1, 4, and 12 weeks after the implantation, the grafts were harvested and gross and histologic examinations were performed. Inflammation grade, graft thickness, neocollagen density, and neocapillary count were measured. Results: The bFGF group displayed more rapid accumulation of inflammatory cells with a higher density of neocapillaries, and increased active collagen synthesis. After 12 weeks, the thickness of the grafts in the control and bFGF groups was $75.15{\pm}4.80%$ and $81.79{\pm}5.72%$, respectively, in comparison to the thickness before transplantation. There was a statistically significant difference between both groups ($p$ <0.05). Conclusion: bFGF was effective in reducing the absorption of acellular human dermal grafts by increasing angiogenesis and accelerating engraftment. In conclusion, bFGF may be a good tool for use in acellular human dermal graft transplantation for reconstructive surgery involving soft-tissue defects.

• Journal of Korean Neurosurgical Society
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• v.44 no.6
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• pp.375-381
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• 2008

Objective : The effects on neural proliferation and differentiation of neural stem cells (NSC) of basic fibroblast growth factor-2 (bFGF). insulin growth factor-I (IGF-I). brain-derived neurotrophic factor (BDNF). and nerve growth factor (NGF) were assessed. Also, following combinations of various factors were investigated : bFGF+IGF-I, bFGF+BDNF, bFGF+NGF, IGF-I+BDNF, IGF-I+NGF, and BDNF+NGF. Methods : Isolated NSC of Fisher 344 rats were cultured with individual growth factors, combinations of factors, and no growth factor (control) for 14 days. A proportion of neurons was analyzed using $\beta$-tubulin III and NeuN as neural markers. Results : Neural differentiations in the presence of individual growth factors for $\beta$-tubulin III-positive cells were : BDNF, 35.3%; IGF-I, 30.9%; bFGF, 18.1%; and NGF, 15.1%, and for NeuN-positive cells was : BDNF, 34.3%; bFGF, 32.2%; IGF-I, 26.6%; and NGF, 24.9%. However, neural differentiations in the absence of growth factor was only 2.6% for $\beta$-tubulin III and 3.1% for NeuN. For $\beta$-tubulin III-positive cells, neural differentiations were evident for the growth factor combinations as follows : bFGF+IGF-I, 73.1 %; bFGF+NGF, 65.4%; bFGF+BDNF, 58.7%; BDNF+IGF-I, 52.2%; NGF+IGF-I, 40.6%; and BDNF+NGF, 40.0%. For NeuN-positive cells : bFGF+IGF-I, 81.9%; bFGF+NGF, 63.5%; bFGF+BDNF, 62.8%; NGF+IGF-I, 62.3%; BDNF+NGF, 56.3%; and BDNF+IGF-I, 46.0%. Significant differences in neural differentiation were evident for single growth factor and combination of growth factors respectively (p<0.05). Conclusion : Combinations of growth factors have an additive effect on neural differentiation. The most prominent neural differentiation results from growth factor combinations involving bFGF and IGF-I. These findings suggest that the combination of a mitogenic action of bFGF and post-mitotic differentiation action of IGF-I synergistically affects neural proliferation and NSC differentiation.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.707-711
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• 1998

The (Na,K)ATPase is responsible for generating the ionic gradients and membrane potentials by the exchange of intracellular $Na^+$ for $K^+$. It has been recentl y shown that (Na,K)ATPase is involved in the exocytic pathway of basic fibroblast growth factor (bFGF), although it is not known that bFGF is secreted to the outside of cell through direct interaction with (Na,K) ATPase. To understand the role for (Na,K)ATPase in the secretary pathway of bFGF, we have sought to identify the cytoplasmic domains of the alpha1 isoform of (Na,K)ATPase interacting with bFGF by yeast two-hybrid system. We have also investigated the interaction between the alpha2 isoform of (Na,K)ATPase and bFGF to find out whether the interaction is isoform-specific. We found that none of the cytoplasmic domains of (Na,K)ATPase isoforms interacted with bFGF. The result suggests that the interaction between bFGF and (Na,K)ATPase might be indirect, thus requiring other proteins which are involved in the formation of protein complexes for the interaction, although we cannot exclude the possibility that the interaction requires the element of the whole alpha subunit structure that was not present in the isolated alpha subunit cytoplasmic domains.

• BMB Reports
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• v.38 no.3
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• pp.290-293
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• 2005

In order to investigate the epitope of basic fibroblast growth factor (bFGF) and its immunogenicity, the epitopes of bFGF were screened from the phage display library with monoclonal antibody GF22, which can neutralize the bio-activity of bFGF. By three rounds of screening, the positive phage clones with bFGF epitopes were selected, which can effectively block the bFGF to bind with GF22. Sequence analysis showed that the epitopes shared a highly conservative sequence (Leu-Pro-Pro/Leu-Gly-His-Phe/Ile-Lys). The sequence of PPGHFK was located at 22-27 of the bFGF. The specific immuno-response of mouse could be highly induced by phage clones with the epitopes. And the anti-bFGF activity induced by LPGHFK was 3 times higher than the original sequence, which showed that the mimetic peptide LPLGHIK might be used as a tumor vaccine in the prevention and treatment of tumor.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.1
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• pp.1-8
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• 2001

This study was designed to localize the distribution of basic fibroblast growth factor(bFGF) in the developing rat condylar region and to elucidate the associated function of bFGF in the condyle development. The condyles of temporomandibular joint of Sprague-Dawley rats (27g of weight) were used. The tissues were examined with electron microscope and immunohistochemical method. The results were as follows: 1. The developing condylar region are divided in to 5 zones apparently: proliferative, maturation, hypertrophic, calcifying, and ossification zones. 2. The cells in the proliferative zone are condensed and have under-developed cell organells in the cytoplasm. This zone shows a strong immunoreactivity of bFGF. 3. The cells in the maturation zone are typical chondroblasts showing well-developed cell organells and round nucleus. The cartilaginous matrix does not show the immunoreactivity of bFGF, while the chondroblasts show the immunoreactivity. 4. The cells in the hypertrophic zone show hypertrophic change having the degenerated cell organelles and small nucleus. There are no immunoreactivity of bFGF in this zone except the nucleus and endoplasmic region showing mild immunoreactivity. 5, The cells in the calcifying zone show hypertrophic change and cell organelles are disappeared. The cells are surrounded by the calcified cartilaginous matrix. There are no immunoreactivity of bFGF in this zone except the endoplasmic region showing mild immunoreactivity. 6. In the zone of bone formation, chondroblasts are disappeared. Newly differentiated osteoblasts secreting osteoid around the calcified cartilaginous matrix. The bone marrow shows the immunoreactivity of bFGF, while the bone matrix does not show the immunoreactivity of bFGF.