• Asian-Australasian Journal of Animal Sciences
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• v.10 no.2
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• pp.233-239
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• 1997

A mammary epithelial cell line (MAC-T) established as a model for lactation was utilized to identify and characterize effects of various hormones upon insulin-like growth factor binding protein secretion. Ligand and immunoblot analyses of conditioned media indicated that insulin-like growth factor binding protein-2 was secreted by MAC-T cells. Insulin-like growth factor-I stimulated insulin-like growth factor binding protein-2 secretion in a dose-dependent manner, but prolactin and bovine somatotropin did not alter insulin-like growth factor binding protein-2 secretion. Insulin increased and cortisol decreased insulin-like growth factor binding protein-2 secretion. Effects of insulin-like growth factor-I on insulin-like growth factor binding protein-2 secretion support previous studies using primary cultures of bovine mammary cells and bovine fibroblasts. Effects of cortisol and insulin on insulin-like growth factor binding protein-2 secretion may be explained by changes in protein synthesis. In addition, supraphysiological doses of insulin can cross-react with the insulin-like growth factor-I receptor and stimulate insulin-like growth factor binding protein-2 secretion. MAC-T cells provide a model system to study mechanisms that regulate local insulin-like growth factor-I bioactivity.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.5
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• pp.363-369
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• 2005

Purpose: To determine the role of Insulin-like Growth Factor-I (IGF-I) in the regulation of Vascular Endothelial Growth Factor (VEGF) expression in MG-63 cells and then to find the mechanism b which this regulation occurs. Materials and methods: MG-63 cells were grown to confluence in 60-mm dishes. To determine the effects of IGF-I on expression of VEGF mRNA according to time and concentration, the cells were treated with 10 nM IGF-I, following isolation of total RNA and Northern blot analysis after 1, 2, 4, 8, 12, 24 hours and after 2 hours of treatment with 0.5, 2, 10, 25, 50 nM IGF-I respectively, isolation of total RNA and Northern blot analysis were followed. To determine the mechanism of action of IGF-I, inhibitors such as hydroxyurea $(76.1\;{\mu}g/ml)$, actinomycin D $(2.5\;{\mu}g/ml)$, cycloheximide $(10\;{\mu}g/ml)$ were added 1 hour after treatment of 10 nM IGF-I. Results: 1. the expression of VEGF mRNA was increased with treatment of IGF-I. 2. The expression of VEGF mRNA was increased according to time-and concentration dependent manner of IGF-I. 3. The effect of IGF-I was decreased by hydroxyuera, actinomycin D, but not by cycloheximide. Conclusion: IGF-I regulate the expression of VEGF mRNA in the level of DNA synthesis and transcription. These results could suggest that IGF-I plays an important role in angiogenesis in the process of new bone formation and remodeling.

• BMB Reports
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• v.38 no.1
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• pp.1-8
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• 2005

Transforming growth factor-$\beta$ is a pleiotropic growth factor that has enthralled many investigators for approximately two decades. In addition to many reports that have clarified the basic mechanism of transforming growth factor-$\beta$ signal transduction, numerous laboratories have published on the clinical implication/application of transforming growth factor-$\beta$. To name a few, dysregulation of transforming growth factor-$\beta$ signaling plays a role in carcinogenesis, autoimmunity, angiogenesis, and wound healing. In this report, we will review these clinical implications of transforming growth factor-$\beta$.

• Molecules and Cells
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• v.39 no.8
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• pp.587-593
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• 2016

As sessile organisms, plants must be able to adapt to the environment. Plants respond to the environment by adjusting their growth and development, which is mediated by sophisticated signaling networks that integrate multiple environmental and endogenous signals. Recently, increasing evidence has shown that a bHLH transcription factor PIF4 plays a major role in the multiple signal integration for plant growth regulation. PIF4 is a positive regulator in cell elongation and its activity is regulated by various environmental signals, including light and temperature, and hormonal signals, including auxin, gibberellic acid and brassinosteroid, both transcriptionally and post-translationally. Moreover, recent studies have shown that the circadian clock and metabolic status regulate endogenous PIF4 level. The PIF4 transcription factor cooperatively regulates the target genes involved in cell elongation with hormone-regulated transcription factors. Therefore, PIF4 is a key integrator of multiple signaling pathways, which optimizes growth in the environment. This review will discuss our current understanding of the PIF4-mediated signaling networks that control plant growth.

• Journal of Periodontal and Implant Science
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• v.21 no.1
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• pp.177.1-177.1
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• 1991

• BMB Reports
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• v.51 no.2
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• pp.73-78
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• 2018

Vascular endothelial growth factor and its receptor (VEGF-VEGFR) system play a critical role in the regulation of angiogenesis and lymphangiogenesis in vertebrates. Each of the VEGF has specific receptors, which it activates by binding to the extracellular domain of the receptors, and, thus, regulates the angiogenic balance in the early embryonic and adult stages. However, de-regulation of the VEGF-VEGFR implicates directly in various diseases, particularly cancer. Moreover, tumor growth needs a dedicated blood supply to provide oxygen and other essential nutrients. Tumor metastasis requires blood vessels to carry tumors to distant sites, where they can implant and begin the growth of secondary tumors. Thus, investigation of signaling systems related to the human disease, such as VEGF-VEGFR, will facilitate the development of treatments for such illnesses.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.1
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• pp.27-34
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• 2009

Angiogenesis is essential for solid tumor growth and progression. Among the pro-angiogenetic factors, vascular endothelial growth factor(VEGF), also known as vascular permeability factor, is the most important as a mitogen for vascular endothelium. The VEGF family of molecules currently consists of six growth factors, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placenta growth factor(PlGF). Over-expression of PlGF is associated with angiogenesis under pathological conditions such as ischemia, inflammation, and cancer. Hence, the goal of this study is to identify the correlation of clinicopathlogical factors and the up-regulation of PlGF expression in oral squamous cell carcinoma. We studied the immunohistochemical staining of PlGF, PlGF gene expression and a real time quantitative RT-PCR in 20 specimens of 20 patients with oral squamous cell carcinoma. The results were as follows. 1. In the immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, the high level staining of PlGF was observed. And the correlation between immunohistopathological PlGF expression and histological differentiation of specimens was significant (Pearson correlation analysis, significance [r] >0.6, P < .05). 2. In the PlGF gene RT-PCR analysis, PlGF expression was more in tumor tissue than in adjacent normal tissue. Paired-samples analysis determined the difference of PlGF mRNA expression level between the cancer tissue and the normal tissue (Student's t - test, P < .05) These findings suggest that up-regulation of the PlGF gene may play a role in progression and local metastasis in invasive oral squamous cell carcinoma.

• Molecules and Cells
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• v.37 no.6
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• pp.487-496
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• 2014

Angiotensinogen (AGT), the precursor of angiotensin I, is known to be involved in tumor angiogenesis and associated with the pathogenesis of coronary atherosclerosis. This study was undertaken to determine the role played by AGT in endothelial progenitor cells (EPCs) in tumor progression and metastasis. It was found that the number of EPC colonies formed by AGT heterozygous knockout ($AGT^{+/-}$) cells was less than that formed by wild-type (WT) cells, and that the migration and tube formation abilities of $AGT^{+/-}$ EPCs were significantly lower than those of WT EPCs. In addition, the gene expressions of vascular endothelial growth factor (VEGF), Flk1, angiopoietin (Ang)-1, Ang-2, Tie-2, stromal derived factor (SDF)-1, C-X-C chemokine receptor type 4 (CXCR4), and of endothelial nitric oxide synthase (eNOS) were suppressed in $AGT^{+/-}$ EPCs. Furthermore, the expressions of hypoxia-inducible factor (HIF)-$1{\alpha}$and $-2{\alpha}$ were downregulated in $AGT^{+/-}$ early EPCs under hypoxic conditions, suggesting a blunting of response to hypoxia. Moreover, the activation of Akt/eNOS signaling pathways induced by VEGF, epithelial growth factor (EGF), or SDF-$1{\alpha}$ were suppressed in $AGT^{+/-}$ EPCs. In $AGT^{+/-}$ mice, the incorporation of EPCs into the tumor vasculature was significantly reduced, and lung tumor growth and melanoma metastasis were attenuated. In conclusion, AGT is required for hypoxia-induced vasculogenesis.

• IMMUNE NETWORK
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• v.11 no.4
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• pp.223-226
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• 2011

Although exercise-induced growth factors such as Insulin-like growth factor-I (IGF-I) are known to affect various aspects of physiology in skeletal muscle cells, the molecular mechanism by which IGF-I modulates anti-inflammatory effects in these cells is presently unknown. Here, we showed that IGF-I stimulation suppresses the expression of toll-like receptor 4 (TLR4), a key innate immune receptor. A pharmacological inhibitor study further showed that PI3K/Akt signaling pathway is required for IGF-I-mediated negative regulation of TLR4 expression. Furthermore, IGF-I treatment reduced the expression of various NF-${\kappa}B$-target genes such as TNF-${\alpha}$ and IL-6. Taken together, these findings indicate that the anti-inflammatory effect of exercise may be due, at least in part, to IGF-I-induced suppression of TLR4 and subsequent downregulation of the TLR4-dependent inflammatory signaling pathway.

• Archives of Pharmacal Research
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• v.29 no.3
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• pp.249-255
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• 2006

Ability of iron acquisition of pathogenic microorganisms functions as a virulence factor. Candida albicans, a fungal pathogen that requires iron for growth, is susceptible to growth retardation by high-affinity iron binding proteins such as transferrin. Recently, we reported that C. albicans could utilize the heme as a part of heme-containing proteins dissociated by heme oxygenase, CaHMX1. In search of another pathway that C. albicans can use to bypass the growth regulation produced by iron limitation, this present study examined utilization of non-candidal siderophores such as Desferal and rhodotorulic acid (RA) for acquisition of inorganic iron by the fungus. C. albicans secreting no siderophores was cultured in iron-free (pretreated with apotransferrin for 24 h) (culture medium). Once growth of the yeast reached stasis from iron starvation, a siderophore was added to the culture media. Results showed that cultures containing apotransferrin within a dialysis membrane recovered growth to the level of untreated controls, whereas C. albicans yeast cells in direct contact with soluble iron-free (apo) transferrin recovered growth only partially. When static growth from iron limitation was reached, the addition of siderophore-apotransferrin complex to culture medium also permitted the yeast to recover growth from apotransferrin growth regulation. All the data show that C. albicans can utilize the non-candidal siderophores for iron acquisition under transferrin regulation as can pathogenic bacteria.