• Journal of Periodontal and Implant Science
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• v.31 no.4
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• pp.787-801
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• 2001

The molecular mechanisms control the function of PDL(periodonta1 ligament) cells and/or fibroblasts remain unclear. PDLsl7, PDL-specific gene, had previousely　identified the cDNA for a novel protein from cultured　PDL fibroblasts using subtraction hybridization between gingival fibroblasts and　PDL fibroblasts. The purpose　of this study was to determine the regulation by growth factors and cytokines on　PDLsl7 gene expression in　cultured human periodontal ligament cells and observe the immunohistochemical　localization of PDLsl7 protein in various tissues of mouse. Primary PDL fibroblasts isolated by scraping the root of the extracted human mandibular third molars. The cells were incubated with various concentration of human recombinant $IL-1{\beta}$, PDGF-BB and TGF\;${\beta}$ for 48h nd 2 weeks. At each time point total RNA was extracted and the levels of transcription ere assessed by reverse transcription-polymerase chain reaction (RT-PCR assay). polyclonal antiserum raised against PDLsl7 peptides, CLSVSYNRSYQINE and SEAVHETDLHDGC, were made, and stained the tooth, periodontium, developing bone, bone marrow and mid-palatal suture of the mouse. The results were as follows. 1. PDLsl7 mRNA levels were increased in response to PDGF (10ng/ml) and $TGF\;{\beta}$(20ng/ml) after treatment of the $IL-1{\beta}$, PDGF-BB and $TGF{\beta}$for 48 h. 2. PDLsl7 was up-regulated only by $TGF{\beta}$(20 ng/ml) after treatment of the $IL-1{\beta}$, PDGF-BB and $TGF\;{\beta}$ for 2 weeks and unchanged by the other stimulants. 3. PDLsl7 was a novel protein coding the 142 amino acid peptides in the ORF and the nucleotide sequences of the obtained cDNA from RT-PCR was exactly same as the nucleotides of the database. 4. Immunohistochemical analysis showed that PDLsl7 is preferentially expressed in the PDL, differentiating osteoblast-like cells and stromal cells of the bone marrow in the adult mouse. 5. The expression of PDLsl7 protein was barely detectable in gingival fibroblasts, hematopoetic cells of the bone marrow and mature osteocytes of the alveolar bone. These results suggest that PDLsl7 might upregulated by PDGF-BB or $TGF{\beta}$ and acts at the initial stage of differentiation when the undifferentiated mesenchymal cells in the bone marrow and PDL differentiate into multiple cell types. However, more research needs to be performed to gain a better understanding of the exact function of PDLsl7 during the differentiation of bone marrow mesenchymal and PDL cells.

• 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.

• Molecules and Cells
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• v.39 no.8
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• pp.625-630
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• 2016

The RNA-binding protein Rbfox3 is a well-known splicing regulator that is used as a marker for post-mitotic neurons in various vertebrate species. Although recent studies indicate a variable expression of Rbfox3 in non-neuronal tissues, including lung tissue, its cellular function in lung cancer remains largely unknown. Here, we report that the number of RBFOX3-positive cells in tumorous lung tissue is lower than that in normal lung tissue. As the transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway is important in cancer progression, we investigated its role in RBFOX3 expression in A549 lung adenocarcinoma cells. TGF-${\beta}1$ treatment inhibited RBFOX3 expression at the transcriptional level. Further, RBFOX3 depletion led to a change in the expression levels of a subset of proteins related to epithelial-mesenchymal transition (EMT), such as E-cadherin and Claudin-1, during TGF-${\beta}1$-induced EMT. In immunofluorescence microscopic analysis, mesenchymal morphology was more prominent in RBFOX3-depleted cells than in control cells. These findings show that TGF-${\beta}$-induced RBFOX3 inhibition plays an important role in EMT and propose a novel role for RBFOX3 in cancer progression.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1589-1593
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• 2012

Objective: To investigate liver fibrosis, TGF-${\beta}1$ levels and curative effects on hepatocellular carcinoma (HCC) with small and conventional dose perfusion chemotherapy by transcatheter arterial chemo embolization (TACE). Methods: Thirty-six hepatocellular carcinoma patients not indicated for surgical resection underwent super-selective transcatheter arterial chemoembolization, divided into small dose (n=15) and conventional dose (n=21) chemotherapy groups. Results: With conventional doses, four indices of liver fibrosis focusing on hyaluronate acide (HA), human procollagen type-III (hPC-III), collagen type-Ⅳ (Ⅳ-C) and transforming growth factor-${\beta}l$ (TGF-${\beta}1$) were obviously increased postoperative compared with preoperative (P<0.01); in contrast, with small doses there were no significant differences except for TGF-${\beta}1$. Five year survival demonstrated no significant differences between the two groups (P>0.05). Conclusion: To hepatocellular carcinoma patients treated by TACE, reducing doses of chemotherapy drugs can reduce progress of liver fibrosis, without impacting on five year survival.

• Laboraroty Animal Research
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• v.33 no.2
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• pp.76-83
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• 2017

Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of $Pycnogenol^{(R)}$ (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in $TGF-{\beta}1$/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.

• The Korea Journal of Herbology
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• v.28 no.4
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• pp.49-55
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• 2013

Objectives : Mori Folium was popularly used as one of the traditional medicinal herbs. Although M. Folium has been cultivated for rearing silkworm historically, it's use has been expanded as natural therapeutic agent for the treatment of filariasis, diabetes and dropsy in East Asia. However, little has been known about the effect of M. Folium on liver fibrosis. Therefore, we would like to explore an anti-fibrogenic potential of M. Folium extract (MFE) using immortalized human hepatic stellate cell line, LX-2 cells. Methods : We examined the effects of MFE on the transforming growth factor ${\beta}1$ ($TGF{\beta}1$)-induced liver fibrosis in LX-2 cells. Cell viability, Smad binding element-driven luciferase activity, phosphorylations level of Smad 2/3, and expression level of $TGF{\beta}1$-dependent target genes were monitored in the MFE-treated LX-2 cells. Results : Up to 30 ${\mu}g/ml$ MFE treatment did not show any possible toxic effect in LX-2 cells. MFE inhibited $TGF{\beta}1$-inducible Smad binding element-driven luciferase activity and decreased the $TGF{\beta}1$-inducible phosphorylations of Smad 2 and Smad 3 in hepatic stellate cell in a dose dependent manner. Furthermore, increases of plasminogen activator inhibitor type 1, $TGF{\beta}1$ and matrix metalloproteinases 2 genes by $TGF{\beta}1$ were also attenuated by MFE treatment. Conclusions : These findings suggested that MFE would be used as a potential therapeutic agent for the treatment liver fibrosis, which might be mediated by the inhibition of $TGF{\beta}1$-inducible Smad 2/3 transactivation and target genes expression.

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.18-24
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• 2005

Background : Endobronchial tuberculosis often complicates bronchostenosis, which can cause dyspnea due to an airway obstruction, and can be misdiagnosed as bronchial asthma or lung cancer. This study investigated the possible correlation between the $interferon-{\gamma}$($IFN-{\gamma}$) and transforming growth $factor-{\beta}$($TGF-{\beta}$) levels in the serum and bronchial washing fluid and the treatment results in endobronchial tuberculosis patients. Methods : Sixteen patients, who were diagnosed as endobronchial tuberculosis using bronchoscopy, and 10 healthy control subjects were enrolled in this study. The $IFN-{\gamma}$ and $TGF-{\beta}$ levels were measured in the serum and bronchial washing fluid of 16 endobronchial tuberculosis patients before and after treatment using the ELISA method. The endobronchial tuberculosis patients were divided into those who showed bronchial fibrostenosis after treatment and those who did not. Results : The $IFN-{\gamma}$ and $TGF-{\beta}$ levels in the bronchial washing fluid in endobronchial tuberculosis patients were elevated comparing to the control (p<0.05). After treatment, 7 of the 16 endobronchial tuberculosis patients showed bronchial fibrostenosis and the other 9 cases healed without this sequela. In the patients with fibrostenosis after treatment, the initial serum $TGF-{\beta}$ level was lower than the patients without fibrostenosis after treatment (p<0.05). Moreover, the serum $TGF-{\beta}$ level after treatment further decreased comparing to the patients without fibrostenosis after treatment(p<0.05). Conclusion : Elevated $IFN-{\gamma}$ and $TGF-{\beta}$ levels in the bronchial washing fluid in endobronchial tuberculosis patients are believed to be related to the pathogenesis of endobronchial tuberculosis. The decreased initial serum $TGF-{\beta}$ level and the change in the serum $TGF-{\beta}$ level after treatment are believed to be involved in bronchial fibrostenosis during the course of the disease.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.3
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• pp.335-341
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• 2003

Carcass weight and backfat thickness are two of important elements in determining the carcass trait in pigs and are studied on animal genetics, nutrition, and endocrinology. Growth factors stimulate or inhibit the proliferation and differentiation of various cells. In particular, insulin-like growth factors (IGFs), transforming growth factor (TGF)-$\beta$, and epidermal growth factor (EGF) are involved in the growth and maintenance of muscle. Also, dehydroepiandrosterone-sulfate (DHEA-S) and cortisol are known to be related to the obesity and subcutaneous fat depth in pigs. Therefore, this study was performed to relate growth factors (IGFs, TGF-${\beta}1$, and EGF) and hormones (cortisol and DHEA-S) concentrations at antemortem and postmortem periods to carcass traits including carcass weight and backfat thickness. Blood and m. Longissimus were collected in pigs at antemortem (30 days before slaughter) and postmortem periods. After slaughtered, carcass weight and backfat thickness were measured. Growth factors and hormones in serum and m. Longissimus were measured by radioimmunoassay or enzyme-linked imuunosorbent assay. Before antemortem period, serum IGF-I and -II concentrations were positively correlated with the carcass weight and backfat thickness in gilts, and the concentrations of TGF- ${\beta}1$ and cortisol in barrows show the correlation with only carcass weight. Also, the positive correlations of muscular IGFs and TGF-${\beta}1$ at postmortem 45 min with the carcass weight and backfat thickness were detected. Consequently, these results suggest that the serum and muscular endocrine factors are involved in the carcass weight and backfat thickness in pigs.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.57-61
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• 2002

The renoprotective activities of white ginseng radix and rootlet were compared in spontaneously hypertensive rat (SHR) with diabetes. During oral administration of white ginseng radix (Ginseng Radix Alba, GRA) and white ginseng rootlet (Ginseng Radix Palva, GRP) for four weeks, arterial blood pressure and blood glucose levels were determined at every 10 days. In both GRA- and GRP-treatment groups, arterial blood pressures started to go down after 10 days of administration and maintained throughout the study period. After four weeks administrations of GRA and GRP, diastolic blood pressures were significantly decreased with 17% and 9%, respectively. GRA treatment also decreased blood glucose levels after 10 days of administration when compared with diabetic SHR group. At the end of the experiment, serum creatinine (Scr) and blood urea nitrogen (BUN) were not significantly different between the groups, except 62% higher value of BUN in diabetic SHR group when compared with SHR group. In the diabetic SHR group, the excretion of urinary albumin was increased significantly when compared with SHR. The level of urinary albumin in GRA treated group was markedly reduced when compared with diabetic SHR group $(67.8{\pm}4.7\;vs.\;131.3{\pm}13.5\;mg/24\;h).$ To examine the effects of ginseng radices on an overt diabetic nephropathy, index of kidney hypertrophy and transforming growth $factor-{\beta}1\;(TGF-{\beta}1)$ protein levels were evaluated. The glomerular and tubular cells stained positive for $TGF-{\beta}1$ seemed to be more abundant in diabetic SHR than in those with SHR, and GRA treated rats showed somewhat less $TGF-{\beta}1$ protein in glomerular and tubular cells when compared with diabetic SHR. Our results suggest that GRA might be a useful antihypertensive and antidiabetic agent with renoprotective effect.