• Molecules and Cells
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• v.24 no.1
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• pp.139-147
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• 2007

Although transforming growth factors (TGFs) are implicated in the process of endochondral ossification, which is initiated by the differentiation of mesenchymal cells into chondrocytes, it is not clear how $TGF-{\beta}3$ regulates the chondrogenic differentiation of limb bud mesenchymal cells. Here, differential display polymerase chain reaction (DD-PCR) screening and RT-PCR analysis revealed that transcripts of A Disintegrin And Metalloprotease 10 (ADAM 10) decreased during the chondro-inhibitory action of $TGF-{\beta}3$ on cultured chick leg bud mesenchymal cells. Electroporation of ADAM 10 morpholino antisense oligonucleotides inhibited the ectodomain shedding of delta-1, and cell proliferation and subsequent precartilage condensation, in a manner similar to that caused by $TGF-{\beta}3$. The suppression of mesenchymal cell proliferation induced by $TGF-{\beta}3$ and ADAM 10 morpholino antisense oligonucleotides was reversed by activation of ADAM 10 with phorbol 12-myristate 13-acetate (PMA) or knockdown of Notch-1 with siRNA. Collectively, these data indicate that, in cultured chick leg bud mesenchyme cells, $TGF-{\beta}3$ downregulates ADAM 10 and inhibits cell proliferation and subsequent precartilage condensation by inhibiting the ectodomain shedding of delta-1, and that this results in the activation of Notch signaling.

• The Journal of Korean Physical Therapy
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• v.22 no.3
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• pp.87-92
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• 2010

Purpose: The purpose of this study was to investigate the effect of electrical stimulation (ES) on the wound closure rate, collagen deposition, and TGF-${\beta}$1 mRNA expression in skin wound of rat. Methods: Twenty male Sprague-Dawley rats (222~271 g) were randomly divided into ES (n=10) and control group (n=10). The ES group received a cathodal stimulation with 50 V at 100 pps for 30 minutes for 7 days, while the control group was not given electrical stimulation. The wound closure rate, collagen density and TGF-${\beta}$1 mRNA ratio were measured. Results: The mean wound closure rates in the ES and control groups were $83.79{\pm}16.35$% and $51.57{\pm}17.76$%, respectively (p<0.001). The collagen density in the ES and control groups were $46.67{\pm}10.68$% and $25.03{\pm}13.09$%, respectively (p<0.001). The TGF-${\beta}$1 mRNA ratio in the ES and control groups were $1.35{\pm}0.60$ and $0.63{\pm}0.30$, respectively at 6 hours post-wound (p<0.01) and $1.69{\pm}0.47$ and $1.32{\pm}0.28$, respectively, at 7 days post-wound (p<0.05). Conclusions: ES accelerated the wound closure rate of skin incision wounds and was accompanied by an increase in collagen deposition in the regenerating dermis. In addition, ES increased TGF-${\beta}$1 mRNA expression during wound healing process. These findings suggest that ES may activate TGF-${\beta}$1 expression, and may increase synthesis activities of fibroblasts in regenerating skin wounds in rats.

• BMB Reports
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• v.29 no.5
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• pp.405-410
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• 1996

Previous studies have shown that transforming growth factor beta ($TGF-{\beta}$) is a potent regulator of cell growth and differentiation. To study the effects of $TGF-{\beta}$ on cell morphology and cytoskeleton reorganization, we conducted a survey using Mv1Lu mink lung epithelial cells with antibodies to cytoskeletal proteins and an extracellular matrix protein. While the untreated cells showed a cuboidal shape of typical epithelia, the Mv1Lu cells displayed a drastic shape change in the presence of $TGF-{\beta}$. This alteration was most prominent when near-confluent cells were treated with $TGF-{\beta}$. Since the morphology alteration is known to be accompanied by the reorganization of cytoskeletal proteins in other cell types, we investigated the intracellular distribution of the three major cytoskeletal structures: microfilaments, microtubules, and intermediate filaments. In the microfilament system, $TGF-{\beta}$ induced new stress fiber formation, which was caused primarily by the polymerization of cytoplasmic G-actin. However, $TGF-{\beta}$ appeared not to induce any significant changes in microtubular structures and vimentin filaments as determined by indirect fluorescence microscopy. Finally we confirmed the rapid accumulation of fibronectin by immunoblot analysis and chased the protein locations by immunofluorescence microscopy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.3
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• pp.199-203
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• 2007

Several matrix metalloproteinases (MMPs) have been shown to play an important role in the invasion and metastasis of oral squamous cell carcinoma (OSCC). The members of the TGF-$\beta$ signaling pathway are being considered as predictive biomarkers for progressive tumorigenesis and molecular targets for the prevention and the treatment of cancer and metastasis. The aim of the present study was to find the clinical significance of the expression of TGF-${\beta}1$ and MMP-2 related to the regional lymph node metastasis in OSCC. This study included 76 cases of primary OSCC, of which 42 cases showed regional lymph node metastases. Immunohistochemistry was used for the localization of protein. The relation between the expression of each protein and clinical variables was statistically evaluated. In results, the expression of TGF-${\beta}1$ both main mass with lymph node metastasis and without lymph node metastasis was found not to be statistically significant (p>0.05). The expression of MMP-2 was found to be statistically significant related to regional lymph node metastasis (p<0.05). When compared the expression in the metastatic lymph node, TGF-${\beta}1$ was significantly highly expressed than MMP-2 (p<0.05). In conclusion, the expression of MMP-2 was significantly elevated in patients with lymph node metastasis as compared to the patients without lymph node metastasis, which could be useful in predicting the risk of lymph node metastasis in OSCC.

• The Journal of Korean Physical Therapy
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• v.14 no.4
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• pp.87-94
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• 2002

Low intensity laser irradiation is potential physical agent that triggers the muscle regeneration by previous study. In muscle regeneration, a number of growth factors also promotes that is triggered in response to muscle damage. The transforming growth factor(TGF)-$\beta$ is involved in the activation of cell proliferation and the inhibition of cell differentiation in muscle regeneration. This is secreted not only autocrine system but also paracrine and endocrine. Therefore, We investigated that effects of Gallium aluminum arsenide(GaAlAs) diode laser for the expression of TGF-$\beta$ on lumbar spinal cord after extensor digitorum muscle crush injury. After laser irradiation, the immunoreactivity of TGF-$\beta$ was increased bilaterally in gray mater of spinal cord. Especially, in 1 day, experimental group was highed than control, and in 3 day, lateral motor nucleus were storong immunoreactivy of TGF-$\beta$. Also, in 1 and 2 day, TGF-$\beta$ was showed in white mater as well as gray mater, but in 3 day, only showed in gray mater. These data may suggests to the establishment of laser irradiation on spinal cord for skeletal muscle injury.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.2
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• pp.123-130
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• 2005

Many of the molecular and genotypic events taking place at the osteoblast cell level during bone-implant integration are still largely unknown. The objective of this study was to examine expression patterns of TGF-$\beta$ and IGF-I related genes during bone-implant integration. Titanium implants with machined surface were placed into 8 rabbit tibias. At 3rd, 7th, 14th, 28th day after implantation, the expression pattern of TGF-$\beta$ and IGF-I genes in bone with or without implant was examined using reverse transcriptase-polymerase chain reaction (RT-PCR). At the same time, histomorphometric analysis was evaluated, respectively. The bone-to-implant contacts (BIC) of experimental groups were 5.2%, 6.2%, 6.6%, 24.6% at 3rd, 7th, 14th, 28th day. This indicated that newly formed bone increased at the implant surface in bone marrow space after implantation. The expressions of TGF-$\beta$ and IGF-I were higher in implantation groups than untreated control groups during all experimental days. The increased expression of TGF-$\beta$ and IGF-I genes may be associated with the increased bone-to-implant contact. This result provided the evidence for existing biologic differences in tissue response after implantation and helped us to understand molecular biologic processes in tissue-implant integration.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.432-441
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• 2024

Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.190-198
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• 2001

Purpose : It was reported that Captopril (angiotensin converting enzyme inhibitor) had an effect to reduce the pneumonitis and pulmonary fibrosis induced by radiation in rat. We peformed this study to investigate the radioprotective effect and mechanism of Captopril. Methods and Materials : The comparison was made between the radiation only group and the combined Captopril and radiation group by examining histopathologic findings and immunohistochemical stains $(TNF\alpha\;and\;TGF\beta1)$ at 2 and 8 weeks after irradiation. Each group has 8 to 10 rats (Sprague-Dawley). 12.5 Gy of X-ray was irradiated to the left hemithorax in a single fraction. Captopril (50 mg/kg/d) mixed with water was given per oral and continuously from 1 week prior to irradiation up to 8th week of the experiment. Result : In the combined Captopril and radiation group, the histopathologic changes which were hemorrhage into alveolar space, changes of alveolar epithelium, bronchial epithelium and blood vessels, and perivascular edema were less severe than in the radisation only group at 2 weeks. At 8 weeks, the alveolar epithelial changes and perivascular edema were less prominant in the combined Captopril and radiation group. At 2 weeks, the $TNF\alpha$ expression of the combined Captopril and radiation group was markedly decreased at the alveolar epithelium (p<0.01), lymphoid tissue (p=0.06) and the macrophage of alveolar space (p<0.01) compared with the radiation only group. Furthermore the $TGF\beta1$ expression was significantly prominant at the alveolar epithelium (p<0.02) and the macrophage in alveolar space (p<0.02). At 8 weeks, the expression of $TNF\alpha\;and\;TGF\beta1$ of most sites, except $TGF\beta1$ of the macrophage of alveolar space (p=0.09), showed no significant difference between 2 groups. Conclusion : This study revealed that early lung damage induced by irradiation was reduced with the addition of Captopril in the latent and early pneumonitis phase. The expression of $TNF\alpha\;and\;TGF\beta1$ at 2 weeks and $TGF\beta1$ at 8 weeks was further decreased in the combined Captopril and radiation group than the radiation only group. From these results, it may be concluded that the proinflammatoy cytokine $(TNF\alpha)$ and fibrogenic cytokine $(TGF\beta1)$ probably play the role of the radioprotective mechanism in Captopril.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.1
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• pp.49-60
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• 2008

Objective: This study was carried out to investigate the effects of 3-dimensional co-culture of human endometrial cells decidualized with progesterone and TGF-${\beta}1$ on the development of 2-cell mouse embryos. Methods: Stromal and epithelial cells isolated from human endometrial tissue were immunostained for cytokeratin and vimentin. Expression of TGF-${\beta}1$, its receptor-1, -2, integrin-${\beta}3$ and prolactin in mono or co-culture according to three different hormone conditions was investigated by RT-PCR. Differential staining was used to investigate the number of ICM and trophectoderm of hatched mouse blastocysts in different three conditions. Results: The immunohistochemical study was positive for cytokeratin or vimentin and confirmed that epithelial and stromal cells were isolated from endometrial tissue successfully. In co-culture, TGF-${\beta}1$, its receptor-1, integrin-${\beta}3$ and prolactin except TGF-${\beta}1$-r2 were expressed in progesterone dominant condition. The hatching and attaching rate were higher in the co-culture with decidualized cells (p<0.05). However, we observed that lots of the incomplete hatched blactocysts attached on non-decidualized cells. The ICM number of hatched mouse blastocysts was higher in co-culture with decidualized and non decidualized cells than media only culture (p<0.05). The trophectoderm number of hatched blastocyst was higher in the co-culture with decidualized cells than non-decidualized cells or media only culture (p<0.05). Conclusion: The administration of progesterone, estrogen and TGF-$\beta$ could induce decidualization of stromal and epithelial cells isolated from human endometrial tissue using 3-dimensional co-culture, and the decidualization of human endometrial cells could increase the hatching and attaching rate of 2-cell mouse embryos.

• Radiation Oncology Journal
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• v.23 no.3
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• pp.161-168
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• 2005

Purpose: The changed expressions of $TGF-{\beta}1$, as a key cytokine in the fibrotic process, due to melatonin with potent antioxidative effects, were investigated in the irradiated lung using fibrosis-sensitive C57BL/6 mice. Materials and Methods: Female C57BL/6 mice were divided into control irradiation-only, and melatonin (300 mg/kg i.p. 1 hr before irradiation) pretreatment groups. The thoraces of the mice were irradiated with a single dose of 12 Gy. The mRNA expressions of $TGF-{\beta}1$ in the lung tissue 2 and 4 weeks after irradiation were quantified using semiquantitive RT-PCR, and the cellular origin and expression levels of $TGF-{\beta}1$ protein were identified using immunohistochemical staining. Results: The relative mRNA expression levels in the irradiation-only and melatonin pretreatment groups 2 and 4 weeks after irradiation were 1.92- and 1.80-fold (p=0.064) and 2.38- and 1.94-fold (p=0.004) Increased, respectively compared to those in the control group. increased expressions of $TGF-{\beta}1$ protein were prominently detected in regions of histopathologicai radiation injury, with alveolar macrophages and septal epithelial cells serving as important sources of $TGF-{\beta}1$ expression. At 2 and 4 weeks after irradiation, the expression levels of protein were $15.8\%\;vs.\;16.9\%$ (p=0.565) and $36.1\%\;vs.\;25.7\%$ (p=0.009), respectively. Conclusion: The mRNA and protein expressions of $TGF-{\beta}1$ in the lung tissue following thoracic irradiation with 12 Gy were significantly decreased by melatonin pretreatment at 4 weeks. These results indicate that melatonin may have a possible application as an antifibrotic agent in radiation-induced lung injury.