• Development and Reproduction
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• v.12 no.2
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• pp.183-194
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• 2008

A variety of stem cells has been emerging as therapeutic cells that can replace organ transplantation in human liver diseases. The present study focused on whether human eyelid adipose-derived stem cells (HAD) might differentiate into functional hepatocyte-like cells in vitro. HAD were isolated from human eyelid adipose tissue. Effect of dimethyl sulfoxide (DMSO), fibroblast growth factor (FGF)-2 and FGF-4 on the hepatic differentiation of HAD have been examined in vitro. Immunocytochemical analysis and PAS staining showed that HAD cultured in both DMSO and FGF-4 exhibited the most intense staining than HAD of the other experimental groups. These HAD expressed numerous hepatocyte-related genes. Immunoblotting analyses showed that HAD cultured in the presence of DMSO and FGF-4 secreted higher amount of human albumin than HAD cultured in other conditions. Urea analysis also demonstrated that these HAD produced higher amount of urea than any other groups of HAD. In conclusion, combined treatment of DMSO and FGF-4 could effectively induce the functional differentiation of HAD into hepatocyte-like cells.

• BMB Reports
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• v.30 no.3
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• pp.194-199
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• 1997

Previous studies have shown that the HD3 human enterocytic differentiated colon carcinoma cell lines having low $PKC{\beta}$ activity did not respond to diacylglycerol and basic FGF by growth and by activation of pp57 MAP kinase, but undifferentiated cell lines exhibiting high $PKC{\beta}$ activity did. To confirm a role of $PKC{\beta}$ in colonocyte mitogenesis, derivatives of HD3 cell line that stably overexpress a full-length of cDNA encoding the ${\beta}_1$ isoform of human PKC were generated. The abundance and activity of $PKC{\beta}$ in two of the these cell lines, PKC3 and PKC8 were much higher than those in the C1 control cell line that carries the vector lacking the $PKC{\beta}_1\;cDNA$ insert. Following exposure to diacylglycerol or basic FGF, proliferation of PKC3 and PKC8 cells increased about 50%; but this effect was not seen with the control C1 cells. Also, in contrast to the control cells, the $PKC{\beta}_1-overproducing$ cells displayed activation of pp57 MAP kinase when treated with diacylglycerol and basic FGF as undifferentiated cell lines did. These results provide direct evidence that $PKC{\beta}_1$ which plays a key role in mitogenic responses of colon carcinoma cells to diacylglycerol and basic FGF is down-regulated in enterocytic differentiation of colon cells.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.89-96
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• 2023

Uric acid produced by guanine deaminase (GDA) is involved in photoaging and hyperpigmentation. Reactive oxygen species (ROS) generated by uric acid plays a role in photoaging. However, the mechanism by which uric acid stimulates melanogenesis in GDA-overexpressing keratinocytes is unclear. Keratinocyte-derived paracrine factors have been identified as important mechanisms of ultraviolet-induced melanogenesis. Therefore, the role of paracrine melanogenic growth factors in GDA-induced hypermelanosis mediated by uric acid was examined. The relationships between ROS and these growth factors were examined. Primary cultured normal keratinocytes overexpressed with wild type or mutant GDA and those treated with xanthine or uric acid in the presence or absence of allopurinol, H₂O₂, or N-acetylcysteine (NAC) were used in this study. Intracellular and extracellular bFGF and SCF levels were increased in keratinocytes by wild type, but not by loss-of-function mutants of GDA overexpression. Culture supernatants from GDA-overexpressing keratinocytes stimulated melanogenesis, which was restored by anti-bFGF and anti-SCF antibodies. Allopurinol treatment reduced the expression levels of bFGF and SCF in both GDA-overexpressing and normal keratinocytes exposed to exogenous xanthine; the exogenous uric acid increased their expression levels. H₂O₂-stimulated tyrosinase expression and melanogenesis were restored by NAC pretreatment. However, H₂O₂ or NAC did not upregulate or downregulate bFGF or SCF, respectively. Overall, uric acid could be involved in melanogenesis induced by GDA overexpression in keratinocytes via bFGF and SCF upregulation not via ROS generation.

• BMB Reports
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• v.29 no.3
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• pp.205-209
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• 1996

To investigate the role of heparin in keratinocyte growth factor (KGF) and acidic fibroblast growth factor (aFGF) high affinity binding to the KGF receptor (KGFR), a cell free system was established which utilized a secreted chimeric molecule between the KGFR extracellular domain and the immunoglobulin heavy chain Fc domain (KGFR-HFc). KGFR-HFc was purified from NIH 3T3 cells and demonstrated the binding of $[^3H]-heparin$ as well as heparin Sepharose. Scatchard analysis showed that the dissociation constant for heparin binding to KGFR-HFc was 140 nM. High affinity KGF and aFGF binding to KGFR-HFc remained unchanged after treatment with 0.6 M NaCl, which is the concentration sufficient to release any bound heparin to the KGFR-HFc. These results strongly suggest that although the KGFR interacts with heparin, the presence of heparin is not absolutely required for high affinity binding of either KGF or aFGF to the KGFR.

• BMB Reports
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• v.50 no.10
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• pp.487-495
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• 2017

Mammalian inner ear comprises of six sensory organs; cochlea, utricle, saccule, and three semicircular canals. The cochlea contains sensory epithelium known as the organ of Corti which senses sound through mechanosensory hair cells. Mammalian inner ear undergoes series of morphogenesis during development beginning thickening of ectoderm nearby hindbrain. These events require tight regulation of multiple signaling cascades including FGF, Wnt, Notch and Bmp signaling. In this review, we will discuss the role of newly emerging signaling, FGF signaling, for its roles required for cochlear development.

• Animal cells and systems
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• v.7 no.3
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• pp.221-225
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• 2003

The tadpole larva of the ascidian Halocynthia roretzi has two sensory pigment cells in its brain vesicle. To elucidate the temporal requirement for FGF signaling in formation of the pigment cells, embryos were treated with an FGF receptor 1 inhibitor, SU5402, or an MEK inhibitor, U0126 during various embryonic stages. In the present study, it is shown that the embryos treated with SU5402 from the 16-cell stage to the early gastrula stage do not form pigment cells, whereas those treated after the early gastrula stage form pigment cells. In pigment cell formation, embryos suddenly exhibited the sensitivity to SU5402 only for 1 h at the neural plate stage(-4 h after the beginning of gastrulation). When U0126 treatment was carried out at various stages between the 8-cell and late neurula stages, the embryos scarcely formed pigment cells. Pigment cell formation occurred when the embryos were placed in U0126 at early tail bud stage. These results indicate that FGF signaling is involved in pigment cell formation at two separate processes during ascidian embryogenesis, whereas more prolonged period is required for MEK signaling.

• Bulletin of the Korean Chemical Society
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• v.28 no.9
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• pp.1613-1614
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• 2007

• The Journal of Korean Medicine
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• v.26 no.4
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• pp.22-30
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• 2005

Objectives: Recently, angiogenesis has gained an increasing interest as a prognostic factor in breast cancer. In this study we aimed to assess the anti angiogenic effects of HAD, a botanical anticancer remedy which has been prescribed in Daejeon University Oriental Hospital in Korea, on patients with breast carcinoma by measuring the serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF) and platelets levels. Methods: The study included 26 consecutive breast cancer patients (mean age$\pm$standard deviation: 47.5$\pm$8.7 years) with stage II to IV disease who were treated with HAD (mean duration $\pm$ standard deviation: 264.5$\pm$121.6 days). In addition to routine laboratory and staging procedures, serum VEGF, b-FGF levels and platelet counts were determined as antiangiogenic markers. The antiangiogenic effects of HAD were evaluated by analyzing the differences between the values of the antiangiogenic markers before and after the treatment with HAD. Results: Serum b-FGF concentrations were significantly reduced after the treatment with HAD (P=0.042). Serum VEGF concentrations were found to have a somewhat decreasing change, though the change was not statistically significant (P=0.229). Platelet counts had little changes (P=O.80). Conclusions: It is supposed that HAD has effects on decreasing the serum b-FGF levels related with the clinical outcome of breast cancer patients.

• 한국생물공학회:학술대회논문집
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• 2000.11a
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• pp.429-432
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• 2000

Chitosan scaffold is widely applied to drug delivery and tissue engineering. We have developed chitosan scaffolds, with various pore size, by differing freezing temperature and duration of ultraviolet (UV) irradiation, for reconstructing skin equivalent. Chitosan scaffold was coated with type I collagen, fibronectin and basic fibroblast growth factor (bFGF) in various combinations and concentrations, to evaluate the effect of extracellular matrix (ECM) and bFGF on cell adhesion, growth and differentiation of dermal fibroblasts. Human dermal fibroblasts, isolated from newborn foreskin and passaged between 3 and 5, were seeded on the top of scaffolds and cultivated for 2 weeks. We examined the morphology and the secretion of ECM of fibroblasts using scanning electron microsopy (SEM) and histochemistry. A stellate morphology of fibroblasts were seen in all groups. The scaffold coated with either type I collagen and bFGF or type I collagen and fibronectin, however, showed the best condtion of dermal fibroblasts, in that the highest cell number and ECM secretion were seen. On the contrary, scaffolds coated with all three factors, type I collagen, bFGF and fibronectin, showed lower number of cells and ECM secretion than scaffolds with two factors. There was a tendency of dose-dependence in all three factors for fibroblast growth and ECM secretion. In conclusion, we may suggest that chitosan scaffold coated with either type I collagen/bFGF or type I collagen/fibronectin could provide more favorable environment for the growth and differentiation of dermal fibroblasts.

• Journal of Periodontal and Implant Science
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• v.25 no.2
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• pp.239-251
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• 1995

The selective migration, attachment and proliferation of periodontal ligament cells are the desired goal of periodontal regeneration therapy. Fibronectin is well known for an attachment protein for dentin surface. Also, Fibroblast growth factor (FGF) is well known to enhance the periodontal regeneration. The purpose of this study was to evaluation the effect of fibronection and FGF on the attachment rate and the cellular activity. Human gingival fibroblast and periodontal ligament cells were cultured from the teeth extracted for non-periodontal reson. Cultured human gingival fibroblast and periodontal ligament cells in vitro were treated with fibronectin and FGF a various dosage and culture times. Cellular activity was examined by MTT assay. The results of this study was demonstrated that cell attachment rate of experimental group was under the control value at 1st, 2nd, 3rd incubation day. But, at 3rd incubation day, attchment value tended to return to the control value. In case of fibronectin alone application, cellular activity was decreased than that of control at 1st, 2nd incubation day. But 3rd day, cellular activity was returned to the control value. The activity of gingival fibroblast in FGF alone application was decreased thatn that of control at each incubation day. But activity of periodontal cell group was increased cell activities at 2nd, 3rd day. Additionally cellular activity of fibronectin & FGF combined application on gingival fibroblast group was similar to control value at incubation day. But activity of periodontal ligament cell group was increased at 2nd, 3rd day compared with control group.This study demonstrated that combined application of fibronectin & FGF induced the selective chemotaxis for periodontal ligament cell in vitro.