• Journal of dental hygiene science
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• v.12 no.6
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• pp.689-695
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• 2012

The aim of this study was to elucidate the effects of concentrated growth factors (CGFs) on human gingival fibroblasts in vitro. Blood was collected from three male volunteers (average age 27 years). CGFs were prepared using standard protocols. The CGF exudates were collected at the following culture time points: 1, 7, 14, and 21 days. The levels of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor ${\beta}1$ (TGF-${\beta}1$) in CGFs were quantified. The CGF exudates were then used to culture human gingival fibroblasts. The biologic characteristics of these fibroblasts were analyzed in vitro for 21 days. Platelet-rich plasma released the highest amounts of TGF-${\beta}1$ and PDGF-BB on the first day. The level of TGF-${\beta}1$ had decreased slightly by day 7, although the difference compared to levels at day 1 was not statistically significant. However, by days 14 and 21, levels of TGF-${\beta}1$ had dropped significantly compared to day 1 levels. The levels of PDGF-BB at days 7, 14, and 21 did not differ significantly from that measured on day 1. CGFs maintained the release of autologous growth factors for a reasonable period of time (7 days for TGF-${\beta}1$ and 21 days for PDGF-BB). Gingival fibroblasts treated with CGF exudates collected at day 14 reached peak viability and synthesized type I collagen. Furthermore, the CGF exudates exerted positive effects on the proliferation and differentiation of these cells at days 1, 7, 14, and 21. The findings of this study suggest that treatment with CGFs represents a promising method of enhancing mucosal healing following surgical procedures.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.5
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• pp.347-355
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• 2022

Abdominal aortic aneurysm (AAA) is a life-threatening disorder worldwide. Fibroblast growth factor 21 (FGF21) was shown to display a high level in the plasma of patients with AAA; however, its detailed functions underlying AAA pathogenesis are unclear. An in vitro AAA model was established in human aortic vascular smooth muscle cells (HASMCs) by angiotensin II (Ang-II) stimulation. Cell counting kit-8, wound healing, and Transwell assays were utilized for measuring cell proliferation and migration. RT-qPCR was used for detecting mRNA expression of FGF21 and activating transcription factor 4 (ATF4). Western blotting was utilized for assessing protein levels of FGF21, ATF4, and markers for the contractile phenotype of HASMCs. ChIP and luciferase reporter assays were implemented for identifying the binding relation between AFT4 and FGF21 promoters. FGF21 and ATF4 were both upregulated in Ang-II-treated HASMCs. Knocking down FGF21 attenuated Ang-II-induced proliferation, migration, and phenotype switch of HASMCs. ATF4 activated FGF21 transcription by binding to its promoter. FGF21 overexpression reversed AFT4 silencing-mediated inhibition of cell proliferation, migration, and phenotype switch. ATF4 transcriptionally upregulates FGF21 to promote the proliferation, migration, and phenotype switch of Ang-II-treated HASMCs.

• 대한두경부종양학회:학술대회논문집
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• 1994.11a
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• pp.21.1-21.1
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• 1994

• Journal of Life Science
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• v.30 no.7
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• pp.640-650
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• 2020

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF protein family which is highly synthesized in the liver, pancreas, and adipose tissue. Depending on the expression tissue, FGF21 uses endo- or paracrine features to regulate several metabolic pathways including glucose metabolism and energy homeostasis. Different physiologically stressful conditions such as starvation, a ketogenic diet, extreme cold, and mitochondrial dysfunction are known to induce FGF21 synthesis in various tissues to exert either adaptive or defensive mechanisms. More specifically, peroxisome proliferator-activated receptor gamma and peroxisome proliferator-activated receptor alpha control FGF21 expression in adipose tissue and liver, respectively. In addition, the pharmacologic administration of FGF21 has been reported to decrease the body weight and improve the insulin sensitivity and lipoprotein profiles of obese mice and type 2 diabetes patients meaning that FGF21 has attracted huge interest as a therapeutic agent for type 2 diabetes, obesity, and non-alcoholic fatty liver disease. However, understanding FGF21 remains complicated due to the paradoxical condition of its tissue-dependent expression. For example, nutrient deprivation largely increases hepatic FGF21 levels whereas adipose tissue-derived FGF21 is increased under feeding condition. This review discusses the issues of interest that have arisen from existing publications, including the tissue-specific function of FGF21 and its action mechanism. We also summarize the current stage of a clinical trial using several FGF21 analogs.

• Archives of Plastic Surgery
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• v.33 no.1
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• pp.1-4
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• 2006

Cryopreserved fibroblast implants represent a major advancement for healing of chronic wounds. Bone marrow stromal cells, which include the mesenchymal stem cells, have a low immunity-assisted rejection and are capable of expanding profoundly in a culture media. Therefore, they have several advantages over fibroblasts in clinical use. The ultimate goal of this study was to compare the wound healing accelerating growth factor secretion of the bone marrow stromal cells with that of the fibroblasts and this pilot study particularly focuses on the growth factor secretion to accelerate wound healing. Bone marrow stromal cells and fibroblasts were isolated from the same patients and grown in culture. At 1, 3, and 5 days post-incubating, secretion of basic fibroblast growth factor(bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta(TGF-${\beta}$) were compared. In TGF-${\beta}$ secretion fibroblasts showed 12~21% superior results than bone marrow stromal cells. In contrast, bFGF levels in the bone marrow stromal cells were 47~89% greater than that in fibroblasts. The VEGF levels of the bone marrow stromal cells was 7~12 fold greater than that of the fibroblasts. Our results suggest that the bone marrow stromal cells have great potential for wound healing accelerating growth factor secretion.

• Molecules and Cells
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• v.19 no.3
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• pp.402-407
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• 2005

Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. To reduce cell loss after transplantation, we introduced the fibroblast growth factor-2 (FGF-2) gene ex vivo before transplantation. The isolated MSCs produced colonies with a fibroblast-like morphology in 2 weeks; over 95% expressed CD71, and 28% expressed the cardiomyocyte-specific transcription factor, Nkx2.5, as well as ${\alpha}$-skeletal actin, Nkx2.5, and GATA4. In hypoxic culture, the FGF-2-transfected MSCs (FGF-2-MSCs) secreted increased levels of FGF-2 and displayed a threefold increase in viability, as well as increased expression of the anti-apoptotic gene, Bcl2, and reduced DNA laddering. They had functional adrenergic receptors, like cardiomyocytes, and exposure to norepinephrine led to phosphorylation of ERK1/2. Viable cells persisted 4 weeks after implantation of $5.0{\times}10^5$ FGF-2-MSCs into infarcted myocardia. Expression of cardiac troponin T (CTn T) and a voltage-gated $Ca^{2+}$ channel (CaV2.1) increased, and new blood vessels formed. These data suggest that genetic modification of MSCs before transplantation could be useful for treating myocardial infarction and end-stage cardiac failure.

• 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.

• 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.

• Molecules and Cells
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• v.40 no.8
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• pp.550-557
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• 2017

The periodontal ligament (PDL) is the connective tissue between tooth root and alveolar bone containing mesenchymal stem cells (MSC). It has been suggested that human periodontal ligament stem cells (hPDLSCs) differentiate into osteo/cementoblast and ligament progenitor cells. The periodontitis is a representative oral disease where the PDL tissue is collapsed, and regeneration of this tissue is important in periodontitis therapy. Fibroblast growth factor-2 (FGF-2) stimulates proliferation and differentiation of fibroblastic MSCs into various cell lineages. We evaluated the dose efficacy of FGF-2 for cytodifferentiation of hPDLSCs into ligament progenitor. The fibrous morphology was highly stimulated even at low FGF-2 concentrations, and the expression of teno/ligamentogenic markers, scleraxis and tenomodulin in hPDLSCs increased in a dose dependent manner of FGF-2. In contrast, expression of the osteo/cementogenic markers decreased, suggesting that FGF-2 might induce and maintain the ligamentogenic potential of hPDLSCs. Although the stimulation of tenocytic maturation by $TGF-{\beta}1$ was diminished by FGF-2, the inhibition of the expression of early ligamentogenic marker by $TGF-{\beta}1$ was redeemed by FGF-2 treatment. The stimulating effect of BMPs on osteo/cementogenesis was apparently suppressed by FGF-2. These results indicate that FGF-2 predominantly differentiates the hPDLSCs into teno/ligamentogenesis, and has an antagonistic effect on the hard tissue differentiation induced by BMP-2 and BMP-4.

• Annals of Pediatric Endocrinology and Metabolism
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• v.23 no.4
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• pp.204-209
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• 2018

Purpose: Growth hormone transduction defect (GHTD) is characterized by severe short stature, impaired STAT3 (signal transducer and activator of transcription-3) phosphorylation and overexpression of the cytokine inducible SH2 containing protein (CIS) and p21/CIP1/WAF1. To investigate the role of p21/CIP1/WAF1 in the negative regulation of the growth hormone (GH)/GH receptor and Epidermal Growth Factor (EGF)/EGF Receptor pathways in GHTD. Methods: Fibroblast cultures were developed from gingival biopsies of 1 GHTD patient and 1 control. The protein expression and the cellular localization of p21/CIP1/WAF1 was studied by Western immunoblotting and immunofluorescence, respectively: at the basal state and after induction with $200-{\mu}g/L$ human GH (hGH) (GH200), either with or without siRNA CIS (siCIS); at the basal state and after inductions with $200-{\mu}g/L$ hGH (GH200), $1,000-{\mu}g/L$ hGH (GH1000) or 50-ng/mL EGF. Results: After GH200/siCIS, the protein expression and nuclear localization of p21 were reduced in the patient. After successful induction of GH signaling (control, GH200; patient, GH1000), the protein expression and nuclear localization of p21 were reduced. After induction with EGF, p21 translocated to the cytoplasm in the control, whereas in the GHTD patient it remained located in the nucleus. Conclusion: In the GHTD fibroblasts, when CIS is reduced, either after siCIS or after a higher dose of hGH (GH1000), p21's antiproliferative effect (nuclear localization) is also reduced and GH signaling is activated. There also appears to be a positive relationship between the 2 inhibitors of GH signaling, CIS and p21. Finally, in GHTD, p21 seems to participate in the regulation of both the GH and EGF/EGFR pathways, depending upon its cellular location.