• Journal of Korean Neurosurgical Society
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• v.30 no.1
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• pp.5-11
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• 2001

Objectives and Importance : The present study investigated the levels of basic fibroblast growth factor(bFGF) in the CSF of patients with moyamoya disease and its clinical significance. Methods : The levels of bFGF in CSF, taken from 26 hemispheres of 14 moyamoya patients and 20 patients without vascular anomaly(control group), were measured by an enzyme-linked immunosorbent assay. We analyzed the correlation between the level of bFGF and the clinical factors such as age, onset pattern, development of neovascularization, and cerebral circulation. Results : The CSF of moyamoya patients contained a high concentration of bFGF to a significant extent. The bFGF level was apparently elevated in the patients in whom neovascularization from indirect revascularization, such as modified encephalo-duro-arterio-synangiosis(EDAS) was well developed. A linear correlation between the values of bFGF and clinical progression was noted. Conclusions : The elevation of bFGF in moyamoya disease seems to be specific. Clinically, the bFGF level may be considered a useful indicator to predict the efficacy of indirect revascularization.

• Journal of Microbiology and Biotechnology
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• v.17 no.10
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• pp.1661-1669
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• 2007

Gamma-aminobutyric acid (GABA) is a non-protein amino acid. It is well known for its role as an inhibitory neurotransmitter of developing and operating nervous systems in brains. In this study, a novel function of GABA in the healing process of cutaneous wounds was presented regarding anti-inflammation and fibroblast cell proliferation. The cell proliferation activity of GABA was verified through an MTT assay using murine fibroblast NIH3T3 cells. It was observed that GABA significantly inhibited the mRNA expression of iNOS, IL-$1{\beta}$, and TNF-${\alpha}$ in LPS-stimulated RAW 264.7 cells. To evaluate in vivo activity of GABA in wound healing, excisional open wounds were made on the dorsal sides of Sprague-Dawley rats under anesthesia, and the healing of the wounds was apparently assessed. The molecular aspects of the healing process were also investigated by hematoxylineosin staining of the healed skin, displaying the degrees of re-epithelialization and linear alignment of the granulation tissue, and immunostaining and RT-PCR analyses of fibroblast growth factor and platelet-derived growth factor, implying extracellular matrix synthesis and remodeling of the skin. The GABA treatment was effective to accelerate the healing process by suppressing inflammation and stimulating re-epithelialization, compared with the epidermal growth factor treatment. The healing effect of GABA was remarkable at the early stage of wound healing, which resulted in significant reduction of the whole healing period.

• 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.

• BMB Reports
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• v.49 no.8
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• pp.437-442
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• 2016

We aimed to study the role of protein L-isoaspartyl methyltransferase (PIMT) in neuronal differentiation using basic fibroblast growth factor (bFGF)-induced neuronal differentiation, characterized by cell-body shrinkage, long neurite outgrowth, and expression of neuronal differentiation markers light and medium neurofilaments (NF). The bFGF-mediated neuronal differentiation of PC12 cells was induced through activation of mitogen-activated protein kinase (MAPK) signaling molecules [MAPK kinase 1/2 (MEK1/2), extracellular signal-regulated kinase 1/2 (ERK1/2), and p90RSK], and phosphatidylinositide 3-kinase (PI3K)/Akt signaling molecules PI3Kp110β, PI3Kp110γ, Akt, and mTOR. Inhibitors (adenosine dialdehyde and S-adenosylhomocysteine) of protein methylation suppressed bFGF-mediated neuronal differentiation of PC12 cells. PIMT-eficiency caused by PIMT-specific siRNA inhibited neuronal differentiation of PC12 cells by suppressing phosphorylation of MEK1/2 and ERK1/2 in the MAPK signaling pathway and Akt and mTOR in the PI3K/Akt signaling pathway. Therefore, these results suggested that PIMT was critical for bFGF-mediated neuronal differentiation of PC12 cells and regulated the MAPK and Akt signaling pathways.

• Archives of Plastic Surgery
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• v.38 no.3
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• pp.217-221
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• 2011

Purpose: FGF4 (fibroblast growth factor 4) is a newly characterized gene which was found to be a transforming gene in several cancerous cells. FGF4 expression and amplification has been subsequently observed in several human cancers including stomach cancer, breast cancer, head and neck squamous cell carcinoma, lung cancer and bladder cancer. This study was designed to measure the protein expression of FGF4 in malignant skin cancers. Methods: We examined 8 normal skin tissues and 24 malignant skin tumor tissues which were 8 malignant melanomas, 8 squamous cell carcinomas and 8 basal cell carcinomas. The specimens were analyzed for the protein expression of FGF4 using immunohistochemical staining. To evaluate the amount of expression of FGF4, the histochemical score (HSCORE) was used. Results: FGF4 was expressed more intensely in malignant melanoma, followed by SCC and BCC in immunohistochemistry. The average HSCORE was 0.01 for normal skin, 2.02 for malignant melanoma, 1.28 for squamous cell carcinoma, and 0.27 for basal cell carcinoma, respectively. The expression of FGF4 in malignant melanoma and squamous cell carcinoma was increased in comparison with normal tissues and basal cell cancer, and the difference was statistically significant (p<0.05). The difference between malignant melanoma and squamous cell carcinoma was not statistically significant. Conclusion: These findings provide evidences that the expression of FGF4 plays an important role in malignant melanoma and squamous cell carcinoma progressions. This article demonstrates expression of FGF4 in human skin malignant tumors, and suggests that FGF4 is more expressed in highly aggressive skin tumors.

• Molecules and Cells
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• v.28 no.1
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• pp.13-17
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• 2009

Basic fibroblast growth factor (bFGF) plays an important role in angiogenesis. However, the underlying mechanisms are not clear. $Mg^{2+}$ is the most abundant intracellular divalent cation in the body and plays critical roles in many cell functions. We investigated the effect of bFGF on the intracellular $Mg^{2+}$ concentration ($[Mg^{2+}]_i$) in human umbilical vein endothelial cells (HUVECs). bFGF increased ($[Mg^{2+}]_i$) in a dose-dependent manner, independent of extracellular $Mg^{2+}$. This bFGF-induced $[Mg^{2+}]_i$ increase was blocked by tyrosine kinase inhibitors (tyrphostin A-23 and genistein), phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) and a phospholipase $C{\gamma}$ ($PLC{\gamma}$) inhibitor (U73122). In contrast, mitogen-activated protein kinase inhibitors (SB202190 and PD98059) did not affect the bFGF-induced $[Mg^{2+}]_i$ increase. These results suggest that bFGF increases the $[Mg^{2+}]_i$ from the intracellular $Mg^{2+}$ stores through the tyrosine kinase/PI3K/$PLC{\gamma}$-dependent signaling pathways.

• Journal of Life Science
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• v.14 no.2
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• pp.263-268
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• 2004

The sprouting of vascular endothelial cells is an initial step in angiogenesis. Matrix metalloproteinases can associate with integrin on the surface of endothelial cells, thereby promoting angiogenesis. The purpose of this study was to test if fibroblast growth factor-2 (FGF-2) can regulate the sprouting in porcine pulmonary artery endothelial cells. FGF-2 induced sprouting and secretion of MMP-2 and plasmin. FGF-2 also induced the expression of integrin Mac-1, which is inhibited IS20I. Addition of BB-94, a 2-antiplasmin and IS20I inhibited FGF-2-induced sprouting activity. Therefore, FGF-2-induced sprouting activity in PPAECs may be accomplished by secretion of proteinases such as MMP-2 and plasmin and integrin expression.

• Bulletin of the Korean Chemical Society
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• v.35 no.4
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• pp.1036-1042
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• 2014

In this study, we introduced the RRLR oligopeptide sequences on the surface of polyamidoamine (PAMAM) dendrimer and characterized the physical properties and gene carrier activity of the novel polymer using HEK 293, NIH3T3, and HeLa cells. The RRLR peptide sequences were derived from a mouse fibroblast growth factor 3 (FGF3) protein containing a bipartite NLS motif. The entire sequence of FGF3 is RLRRDAGGRGGVYEHLGGAPRRRK and it has two functional sequences RLRR and RRRK at N-terminus and C-terminus, respectively. In particular, PAMAM G4-RRLR conferred enhanced transfection efficiency and lower cytotoxicity compared with those of PEI 25 kDa, PAMAM G4-R, and PAMAM G4 in various cell lines. These results suggest that the introduction of N-terminal oligopeptides of FGF3 on the surface of PAMAM holds promise as an effective non-viral gene delivery carrier for gene therapy.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.7-13
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• 1999

The stimulatory effect of recombinant human basic fibroblast growth factor (bFGF) on wound healing was evaluated in healing-impaired animal models. Full-thickness wounds were made in prednisolone-treated mice, streptozotocin (STZ)-induced diabetic rats and mitomycin C (MMC)-treated rats. Saline or bFGF at a dose of 1, 5, or $25\mu\textrm{g}$ per wound was applied to the open wound once a day for three to five days. The degree of wound healing was assessed using wound size and histological parameters such as degree of epidermal and dermal regeneration. Local application of bFGF accelerated wound closure significantly in a dose-dependent manner in all healing-impaired wounds (p<0.05). The wound healing effect of bFGF was further confirmed by histological examination in MMC-treated rats. Epidermal and dermal regeneration were enhanced in bFGF-treated wounds with a dose-related response. Dermal regeneration parameters such as collagen matrix formation and angiogenesis were significantly increased in $5\mu\textrm{g}$, or $\25mu\textrm{g}$ of bFGF-treated wounds when compared to saline-treated wounds (p<0.05). pectin immunostaining on day 8 for vascular endothelium showed an increased number of neovessels in bFGF-treated wounds. These results suggest that topical application of bFGF has beneficial effects on wound healing by angiogenesis and granulation tissue formation in healing-impaired wounds.

• 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.