• The korean journal of orthodontics
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• v.30 no.6 s.83
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• pp.713-721
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• 2000

Bone cells produce multiple growth factors and cytokines that have effects on bone metabolism and can be incorporated into the bone matrix. The present study was designed to extend these observations by examining the interactions between transforming growth factor-$\beta$(TGF-$\beta$) or interleukin-$1\beta$(rhIL-$1\beta$) and bone cells in a rat long bone culture model. IL-$1\beta$ regulates several activities of the osteoblast cells derived from rat long bone explants in vitro. IL-$1\beta$ stimulated cellular proliferation as well as the synthesis of prostaglandin $E_2$ and Plasminogen activator activity in the cultured cells in a dose-dependent manner. TGF-$\beta$ is present in the bone matrix and potentially released during bone resorption. TGF-$\beta$ reduced basal bone resorption and inhibited vitamin $D_3[1,25(OH)_2D_3]$-induced bone resorption in rat long bone cells. These results support the role of IL-$1\beta$ in the pathological modulation of bone cell metabolism, with regard to implication in the Pathogenesis of osteoporosis by IL-$1\beta$, and that TGF-$\beta$ positively inhibits the bone resorption.

• Preventive Nutrition and Food Science
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• v.19 no.3
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• pp.136-144
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• 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. This study was conducted to evaluate the effects of Platycarya strobilacea S. et Z. (PSE) extract on mouse hair growth and to determine the mechanism of action of PSE. PSE was purchased and its antioxidant activities, such as electron donating ability, total polyphenol content, and flavonoid content were tested. Toxicity during topical treatment was determined by the CCK-8 assay, a cell viability test. Fifteen 4-week-old male C57BL/6 mice were assigned to receive one of three treatments: dimethyl sulfoxide (negative control), minoxidil (positive control) or PSE. Test materials were topically applied to the shaved dorsal skin of each mouse daily for 3 weeks. After 21 days, we observed skin tissue hair follicle morphology and length, mast cell number, and stem cell factor (SCF) expression using hematoxylin and eosin (H&E), toluidine blue, and immunohistochemical staining, respectively. Furthermore, the expression of cytokines involved in hair growth [i.e., insulin-like growth factor (IGF)-1, keratinocyte growth factor (KGF), and transforming growth factor (TGF)-${\beta}1$] was determined by PCR. PSE was found to have very high antioxidant activity. The cell viability rate of PSE-treated mice was markedly higher than that of mice in the control group. We also observed an increase in hair follicle length, strong SCF staining, and a decrease in mast cell number in the PSE group. In addition, PSE-treated mice had higher IGF-1 and KGF expression and lower TGF-${\beta}1$ expression than mice in the minoxidil-treated group. These results suggest that topical application of PSE promotes hair growth by intensifying SCF, suppressing mast cell production, and increasing hair growth-promoting cytokine expression.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.141-148
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• 2015

Epithelial mesenchymal transition (EMT) is the first step in metastasis and implicated in the phenotype of cancer stem cells. Therefore, understanding and controlling EMT, are essential to the prevention and cure of metastasis. In the present study, we examined, by Western blot, reverse transcription polymerase chain reaction (RT-PCR), and confocal microscopy, the effects of cardamonin (CDN) on transforming growth factor-${\beta}1$ (TGF-${\beta}1$)-induced EMT of A549 lung adenocarcinoma cell lines. TGF-${\beta}1$ induced expression of N-cadherin and decreased expression of E-cadherin. CDN suppressed N-cadherin expression and restored E-cadherin expression. Further, TGF-${\beta}1$ induced migration and invasion of A549 cancer cells, which was suppressed by CDN. TGF-${\beta}1$ induced c-Jun N-terminal kinase (JNK) activation during EMT, but CDN blocked it. Protein serine/threonine phosphatase 2A (PP2A) expression in A549 cancer cells was reduced by TGF-${\beta}1$ but CDN restored it. The overall data suggested that CDN suppresses TGF-${\beta}1$-induced EMT via PP2A restoration, making it a potential new drug candidate that controls metastasis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.42
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• pp.23.1-23.11
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• 2020

Background: 4-Hexylresorcinol (4HR) is able to increase angiogenesis. However, its molecular mechanism in the human endothelial cells has not been clarified. Methods: As endothelial cells are important in angiogenesis, we treated the human umbilical vein endothelial cells (HUVECs) with 4HR and investigated protein expressional changes by immunoprecipitation high-performance liquid chromatography (IP-HPLC) using 96 antisera. Results: Here, we found that 4HR upregulated transforming growth factor-β (TGF-β)/SMAD/vascular endothelial growth factor (VEGF) signaling, RAF-B/ERK and p38 signaling, and M2 macrophage polarization pathways. 4HR also increased expression of caspases and subsequent cellular apoptosis. Mechanistically, 4HR increased TGF-β1 production and subsequent activation of SMADs/VEGFs, RAF-B/ERK and p38 signaling, and M2 macrophage polarization. Conclusion: Collectively, 4HR activates TGF-β/SMAD/VEGF signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.

• Korean Journal of Pharmacognosy
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• v.44 no.2
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• pp.110-117
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• 2013

Cirsium japonicum (CJ) leaf (L) alcoholic extracts were investigated for analysis their active components (flavonoids and flavanolignans; silymarins) and inhibitory effect on transforming growth factor (TGF)-${\beta}$ induced hepatic stellate cells (HSCs, LX-2 cells) activation. The CJ root (R) extracts were also analyzed and compared with leaf extracts. Total flavonoid and polyphenol contents of the leaf extracts showed higher than those of the root extracts. The content of each flavonoid compound, which was analyzed by HPLC, in CJ-L extracts was also higher than in CJ-R extracts. The results of flavanolignans content in CJ-L and CJ-R extracts were consistent in flavonoid and polyphenol. We studied inhibitory effect of two extracts against TGF-${\beta}1$ induced HSCs activation. The CJ-L extracts significantly suppressed overexpression of profibrogenic factor, ${\alpha}$-smooth muscle actin and collagen-${\alpha}1$(I). The CJ-R extract also showed inhibitory effect on TGF-${\beta}1$ induced HSCs activation, but the efficacy was lower than in CJ-L extract. These results suggest that CJ-L may contribute to the fibrotic liver treatment.

• Development and Reproduction
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• v.15 no.2
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• pp.99-111
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• 2011

The present experiment was performed to evaluate the chondrogenic differentiation potential of human adipose tissue-derived mesenchymal stem cells (ATMSCs) in the chondrogenic induction medium (CIM) with transforming growth factor-${\beta}1$ (TGF-${\beta}1$) and to evaluate the chondrogenic differentiation of ATMSCs seeded in gelatin-chondroitinglucosamine scaffold (GCG-scaffold). ATMSCs and mouse chondrocytes were cultured in the basic medium and CIM without TGF-${\beta}1$ (CIM1) or with TGF-${\beta}1$ (CIM2) for chondrogenic differentiation potential. The chondrogenic differentiation of ATMSCs was evaluated by glycosaminoglycan (GAG) synthesis and histochemical staining. In pellet culture, GAG synthesis of ATMSCs and chondrocyte was increased in culture on 14 days, but higher in CIM1 than basic medium, especially highest in CIM2. Cartilage matrix was observed in ATMSCs cultured in CIM2 on 14 days by Safranin O and trichrome staining. In well plate culture, proliferation of ATMSCs was continuously increased in culture on 10 days and higher in CIM than basic medium. The cell adhesion rate of ATMSCs seeded in flask or scaffolds was continuously increased during culture period, but higher in scaffold than flask. GAG synthesis of ATMSCs seeded in scaffolds showed no change in control group. In the CIM groups, GAG synthesis of ATMSCs was continuously increased than control group during culture period, especially very high in CIM2 and in the GCG-scaffold was slightly higher than the gelatin scaffold (G-scaffold). The present results demonstrated that ATMSCs showed an low chondrogenic differentiation potential, compared to mouse chondrocytes for 14 days of culture. TGF-${\beta}1$ is important factor in chondrogenic differentiation of ATMSCs. Gelatin scaffold was considered to increasing the effective chondrogenic differentiation environment. ATMSCs seeded in GCG-scaffold was more effective in chondrogenesis than in G-scaffold. Conclusively, the present results demonstrated that the treatment of chondroitin and glucosamine in the scaffold was more effective to promote the cartilage matrix formation.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.4.1-4.19
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• 2018

Transforming growth factor $(TGF)-{\beta}$ signaling is increasingly recognized as a key driver in cancer. In progressive cancer tissues, $TGF-{\beta}$ promotes tumor formation, and its increased expression often correlates with cancer malignancy. In this study, we utilized adenoviruses expressing short hairpin RNAs against $TGF-{\beta}1$ and $TGF-{\beta}2$ to investigate the role of $TGF-{\beta}$ downregulation in cancer cell death. We found that the downregulation of $TGF-{\beta}$ increased the phosphorylation of several SAPKs, such as p38 and JNK. Moreover, reactive oxygen species (ROS) production was also increased by $TGF-{\beta}$ downregulation, which triggered Akt inactivation and NOX4 increase-derived ROS in a cancer cell-type-specific manner. We also revealed the possibility of substantial gene fluctuation in response to $TGF-{\beta}$ downregulation related to SAPKs. The expression levels of Trx and GSTM1, which encode inhibitory proteins that bind to ASK1, were reduced, likely a result of the altered translocation of Smad complex proteins rather than from ROS production. Instead, both ROS and ROS-mediated ER stress were responsible for the decrease in interactions between ASK1 and Trx or GSTM1. Through these pathways, ASK1 was activated and induced cytotoxic tumor cell death via p38/JNK activation and (or) induction of ER stress.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.

• Korean Journal of Poultry Science
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• v.44 no.3
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• pp.211-223
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• 2017

Transforming growth factor beta ($TGF-{\beta}$) signaling pathways are involved in the regulation of proliferation, differentiation, immunity, survival, and apoptosis of many cells. The aim of this study was to investigate the differential expression of $TGF-{\beta}$-related genes, and their interactions and regulators in the spleen of two genetically disparate chicken lines (Marek's disease resistant line 6.3 and Marek's disease-susceptible line 7.2) induced with necrotic enteritis (NE) by Eimeria maxima and Clostridium perfringens infection. By using high-throughput RNA-sequencing, we investigated 76 $TGF-{\beta}$-related genes that were significantly and differentially expressed in the spleens of the chickens. Approximately 20 $TGF-{\beta}$ pathway genes were further verified by qRT-PCR, and the results were consistent with our RNA sequencing data. All 76 identified genes were analyzed through Gene Ontology and mapped onto the KEGG chicken $TGF-{\beta}$ pathway. Our results demonstrated that several key genes, including $TGF-{\beta}$1-3, bone morphogenetic proteins (BMP)1-7, inhibitor of differentiation (ID) proteins ID1-3, SMAD1-9, and Jun, showed a markedly differential expression between the two chicken lines, relative to their respective controls. We then further predicted 24 known miRNAs that targeted BMP7 mRNA from 139 known miRNAs in the two chicken lines. Among these, six miRNAs were measured by qRT-PCR. In conclusion, this study is the first to analyze most of the genes, interactions, and regulators of the $TGF-{\beta}$ pathway in the innate immune responses of NE afflicted chickens.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8143-8147
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• 2014

To investigate the expression intensity and prognostic significance of TGF-${\beta}1$ protein in non-small cell lung cancer (NSCLC), immunohistochemistry was carried out in 194 cases of NSCLC and 24 cases of normal lung tissues by SP methods. The PU (positive unit) value was used to assess the TGF-${\beta}1$ protein expression in systematically selected fields under the microscope with Leica Q500MC image analysis. We found that the TGF-${\beta}1$ PU value was nearly two-fold higher in NSCLC than in normal lung tissues (p=0.000), being associated with TNM stages (p=0.000) and lymph node metastases (p=0.000), but not to patient age, gender, smoking history, tumor differentiation, histological subtype and tumor location (P>0.05). Univariate analysis indicated that patients with high TGF-${\beta}1$ protein expression and lymph node metastases demonstrated a poor prognosis (both p=0.000,). Multivariate analysis showed that TGF-${\beta}1$ protein expression (RR = 2.565, p=0.002) and lymph node metastases (RR=1.874, p=0.030) were also independent prognostic factors. Thus, TGF-${\beta}1$ protein expression may be correlated to oncogenesis and serve as an independent prognostic biomarker for NSCLC.