• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4683-4688
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• 2012

Aim: To investigate the association of transforming growth factor-beta 1 (TGF-${\beta}1$) C-509T polymorphism and susceptibility to cancer by means of meta-analysis. Methods: An extensive search was performed to identify eligible case-control studies investigating such a link. The strength of the association between TGF-${\beta}1$ C-509T polymorphism and cancer risk was assessed by pooled odds ratios (ORs) and 95%confidence intervals (95%CIs) in fixed or random effects models. Results: 55 published case-control studies with a total number of 21,639 cases and 28,460 controls were included. Overall, there was no association between TGF-${\beta}1$ C-509T and cancer risk in all genetic comparison models (TT vs. CC: OR=1.01, 95%CI=0.89-1.15; T vs. C: OR=1.01, 95%CI=0.94-1.07). However, a stratified analysis by cancer type indicated -509 T allele was significantly associated with decreased risk of colorectal cancer (CRC) (TT vs. CT/CC: OR=0.85, 95%CI=0.76-0.95), especially for Caucasians (TT vs. CT/CC: OR=0.83, 95%CI=0.71-0.98) and for population-based studies (TT vs. CT/CC: OR=0.78, 95%CI=0.68-0.89). Conclusion: This meta-analysis suggested that TGF-${\beta}1$ C-509T polymorphism might contribute to a decreased risk on colorectal cancer susceptibility, especially for Caucasians.

• Tuberculosis and Respiratory Diseases
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• 제73권2호
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• pp.84-92
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• 2012

Background: Asian dust storms can be transported across eastern Asia. In vitro, Asian dust particle-induced inflammation and enhancement of the allergic reaction have been observed. However, the fibrotic effects of Asian dust particles are not clear. Production of transforming growth factor ${\beta}_1$ (TGF-${\beta}_1$) and fibronectin were investigated in the bronchial epithelial cells after exposure to Asian dust particulate matter (AD-PM10). Methods: During Asian dust storm periods, air samples were collected. The bronchial epithelial cells were exposed to AD-PM10 with and without the antioxidant, N-acetyl-L-cysteine (NAC). Then TGF-${\beta}_1$ and fibronectin were detected by Western blotting. The reactive oxygen species (ROS) was detected by the measurement of dicholorodihydrofluorescin (DCF), using a FACScan, and visualized by a confocal microscopy. Results: The expression of TGF-${\beta}_1$, fibronectin and ROS was high after being exposed to AD-PM10, compared to the control. NAC attenuated both TGF-${\beta}_1$ and fibronectin expression in the AD-PM10-exposed the bronchial epithelial cells. Conclusion: AD-PM10 may have fibrotic potential in the bronchial epithelial cells and the possible mechanism is AD-PM10-induced intracellular ROS.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5181-5186
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• 2014

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

• Tuberculosis and Respiratory Diseases
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• 제58권1호
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• pp.18-24
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• 2005

연구배경 : 기관지 결핵의 주요 합병증인 기관지 협착은 기도폐쇄에 의한 호흡곤란을 초래하거나 천식이나 폐암으로 오인되는 등의 임상적 문제를 가진다. 본 연구는 기관지 결핵 환자를 대상으로 치료 후 기관지 협착이 발생한 군과 발생하지 않은 군간에 치료 전후의 $IFN-{\gamma}$ 및 $TGF-{\beta}$의 혈청 및 기관지 세척액 농도를 비교함으로써 $IFN-{\gamma}$ 및 $TGF-{\beta}$의 농도와 기관지 협착 발생과의 연관성을 알아보고자 하였다. 대상 및 방법 : 기관지 내시경을 통한 세균학적 검사 및 조직검사로 기관지 결핵으로 진단받은 16명의 환자를 대상으로 치료 전후에 기관지 세척술을 포함한 기관지 내시경술을 시행하였으며 $IFN-{\gamma}$와 $TGF-{\beta}$의 혈청 및 기관지 세척액에서의 농도를 측정하였다. 동일한 방법으로 건강한 성인 대조군 10명에서 혈청 및 기관지 세척액의 $IFN-{\gamma}$와 $TGF-{\beta}$ 농도를 측정하였다. 결 과 : 기관지 결핵 환자군에서 대조군에 비해 기관지 세척액의 $IFN-{\gamma}$(108.55 pg/ml vs undetectable, median)와 $TGF-{\beta}$ 농도(60.80 pg/ml vs undetectable, median)가 유의하게 증가되어 있었다(p<0.05). 치료 후 시행한 기관지 내시경 소견에서 섬유화로 인한 기관지 협착이 남은 환자가 7명 이었고 나머지 9명은 후유증 없이 치유된 소견을 보였다. 기관지 협착을 보인 환자군이 협착이 남지 않은 군에 비해 치료 전의혈청 $TGF-{\beta}$ 농도(847.67 pg/ml vs 1140.30 pg/ml, median)가 낮았으며 또한 치료 후에 더 많이 감소하였다(${\Delta}381.08pg/ml$ vs ${\Delta}191.47pg/ml$, median)(p<0.05). 결 론 : 증가된 기관지 세척액의 $IFN-{\gamma}$와 $TGF-{\beta}$ 농도는 기관지 결핵의 발생기전과 관련이 있을 것으로 생각되며 치료 경과에서 섬유화로 인한 기관지 협착의 발생 유무는 혈청 $TGF-{\beta}$의 치료 전 농도 및 치료 후 농도 변화와 연관성이 있을 것으로 추정된다.

• Asian-Australasian Journal of Animal Sciences
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• 제15권11호
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• pp.1546-1552
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• 2002

Proliferation and differentiation of ovarian cells are regulated by gonadotrophins and various intraovarian factors, with many of their actions dependent on growth factors. Transforming growth factor-$\beta$ (TGF-$\beta$) has been reportedly involved in the regulation of ovarian follicular development. The overall objectives of the present study were to examine the influence of TGF-$\beta$1 expression in ovarian follicular development or yolk formation and to investigate the association of egg weight with ovarian TGF-$\beta$1 expression at 60 wk. Egg weights of 70 Korean Native Ogol Chicken (KNOC) were recorded from 20 to 60 wk. Ovaries were taken at 60 wk, and TGF-$\beta$1 was measured with ELISA, respectively. Based on egg weight up to 60 wk and TGF-$\beta$1 expression in ovary, the chickens were divided into high and low groups. Egg weights and follicle weight in the high TGF-$\beta$1 group were higher than those in the low groups. Also, TGF-$\beta$1 expression and follicle weight in high egg weight group were higher than those in the low groups. Taken together, the results indicate that TGF-$\beta$1 is associated with egg weight in KNOC. This association of TGF-$\beta$1 with egg weight in KNOC supports the report that TGF-$\beta$ is mainly involved in the development and differentiation of follicles in the poultry. Further studies about other endocrine factors related to yolk formation are required to fully understand the endocrine mechanism of egg weight in Korean Native Ogol Chickens.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.4137-4142
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• 2015

The zinc finger transcription factor EGR 1 has a role in controlling synaptic plasticity, wound repair, female reproductive capacity, inflammation, growth control, apoptosis and tumor progression. Recent studies mainly focused on its role in growth control and apoptosis, however, little is known about its role in epithelial-mesenchymal transition (EMT). Here, we aim to explore whether EGR 1 is involved in TGF-${\beta}1$-induced EMT in non-smallcell lung cancer cells. Transforming growth factor (TGF)-${\beta}1$ was utilized to induce EMT in this study. Western blotting, RT-PCR, and transwell chambers were used to identify phenotype changes. Western blotting was also used to observe changes of the expression of EGR 1. The lentivirus-mediated EGR 1 vector was used to increase EGR 1 expression. We investigated the change of migration to evaluate the effect of EGR 1 on non-small-cell lung cancer cells migration by transwell chambers. After stimulating with TGF-${\beta}1$, almost all A549 cells and Luca 1 cells (Non-small-cell lung cancer primary cells) changed to mesenchymal phenotype and acquired more migration capabilities. These cells also had lower EGR 1 protein expression. Overexpression of EGR 1 gene with EGR 1 vector could decrease tumor cell migration capabilities significantly after adding TGF-${\beta}1$. These data s howed an important role of EGR 1 in the EMT of non-small-cell lung cancer cells, as well as migration.

• Journal of Microbiology and Biotechnology
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• 제14권6호
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• pp.1267-1274
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• 2004

Colostrum contains various kinds of cytokines including TGF-$\beta$ that has potent regulatory effects on cells of the immune system. We compared the levels of TGF-$\beta$1 and TGF-$\beta$2 in bovine and human colostrum. Based on the isoform-specific ELISA, bovine colostrum collected on day 1 post-delivery retained $53.71{\pm}29.55\;ng/ml$ of TGF-$\beta$1 and $40.41{\pm}21.78\;{\mu}g/ml$ of TGF-$\beta$2 (n=4), while in human, $381.45{\pm}158.24\;ng/ml$ of TGF-$\beta$1 and $41.47{\pm}9.63\;ng/ml$ of TGF-$\beta$2 (n=5). Thus, dominant TGF-$\beta$ isoforms were completely opposite between human and bovine colostrum samples. The concentrations of both isoforms declined as lactation proceeded. Biological activities of the colostrum samples were determined using an MV1LU cell line. Consistent with the result from the immunoassay, TGF-$\beta$1 in human and TGF-$\beta$2 in bovine colostrum were responsible for the anti proliferative activity against MV1LU cells. Furthermore, bovine colostrum increased IgA secretion by LPS-stimulated mesenteric lymph node (MLN) cells, and this effect was abrogated by either anti­TGF-$\beta$2 antibody or combined anti-TGF-$\beta$1/$\beta$2 antibody, but not by anti- TGF-$\beta$1 antibody alone. Similarly, TGF-$\beta$2 in bovine colostrum enhanced the Ig germ line (GL) promoter activity, which is the earliest event toward IgA isotype switching. Taken together, these results suggest that TGF-$\beta$ isoforms, differentially expressed in human and bovine colostrum, may promote IgA isotype production in the neonatal intestine.

• Journal of Ginseng Research
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• 제43권1호
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• pp.68-76
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• 2019

Background: In colorectal cancer (CRC), 40-60% of patients develop metastasis. The epithelial-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of CRC. The aim of this study was to investigate the effect of Korean Red Ginseng extract (RGE) on colorectal metastasis through inhibition of EMT and the metastatic abilities of CRC cells. Methods: To investigate the effect of RGE on the metastatic phenotypes of CRC cells, CT26 and HT29 cells were evaluated by using an adhesion assay, a wound-healing assay, an invasion assay, zymography, and real-time reverse transcription-polymerase chain reaction. Western-blot analysis was conducted to elucidate the molecular mechanisms of RGE, which showed an inhibitory effect on the transforming growth factor-${\beta}1$ ($TGF-{\beta}1$)-induced EMT in HT29 cells. Additionally, the antimetastatic effect of RGE was evaluated in a mouse model of lung metastasis injected with CT26 cells. Results: RGE decreased the adhesion and migration ability of the CT26 cells and TGF-${\beta}1$-treated HT29 cells. The invasion ability was also reduced by RGE treatment through the inhibition of matrix metalloproteinase-9 expression and activity. Moreover, RGE suppressed the TGF-${\beta}1$-induced EMT via TGF-${\beta}1$/Smad-signaling-mediated Snail/E-cadherin expression in HT29 cells and lung tissue in CT26 tumor-bearing mice. Conclusion: Our results demonstrated that RGE inhibited colorectal lung metastasis through a reduction in metastatic phenotypes, such as migration, invasion, and the EMT of CRC cells.

• Clinical and Experimental Pediatrics
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• 제51권5호
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• pp.523-527
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• 2008

목 적 : HSP는 소아에서 흔한 전신성 혈관염으로 명확한 병인은 밝혀지지 않았으나 염증성 시토카인들이 발병기전에 관여하는 것으로 여겨지며 그중 전환성장인자-${\beta}$가 HSP의 발병기전과 연관이 있는 것으로 보여진다. 본 연구의 목적은 전환성장인자-${\beta}$ 프로모터 유전자의 유전학적 다형성과 HSP 환자에서의 신장 침범과의 관련성을 조사하고자 하는 것이다. 방 법 : 2003년 6월부터 2005년 6월까지 연세대학교 원주기독병원 소아과를 방문하여 HSP로 진단받은 15세 이하 환아 34명과 같은 기간 본원을 방문한 정상 대조군 27명을 대상으로 하였다. 전환성장인자-${\beta}$ 다형성 유전자 표현형은 PCR-RFLP로 환자군과 대조군에서 시행하였다. 결 과 : HSP 환자군과 대조군에서 전환성장인자-${\beta}$ 프로모터 유전자 다형성의 T 대립유전자 빈도는 각각 45%, 48.8% 였으며, T 대립유전자 빈도 간에 통계학적으로 유의한 차이는 없었다(P=0.37). TT 유전자 표현형도 환자군과 대조군에서 빈도의 차이가 없었고(26% vs. 22%, P=0.37), 환자군 중 신장 침범에 있어서도 유의한 차이가 나타나지 않았다(29% vs. 20%, P=0.77). 결 론 : 전환성장인자-${\beta}$ 유전자 다형성의 TT 표현형과 T 대립유전자의 빈도가 HSP 환아의 질병 감수성이나 신장침범과의 연관성을 보임을 관찰할 수 없었으며 HSP 환자들에게 있어서 보다 큰 집단을 대상으로 하는 연구가 전환성장인자-${\beta}$와 신장침범 및 질병 감수성과의 연관성을 명확히 하는데 필요할 것으로 보인다.

• Journal of Periodontal and Implant Science
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• 제25권3호
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• pp.518-528
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• 1995

The immunohistochemical study has been performed on the distribution of receptors for various growth factors in the newly forming granulation tissues following the guided tissue regeneration procedures. Two specimens from 2 different patients were collected from the newly forming granulation tissues at 2 weeks following GTR procedures using Gore-tex menbrane and rubber dam, respectively. For immunohistochemical localization of each recptor, anti-platelet-derived growth factor $receptor-{\alpha}$, anti-platelet-derived growth factor $receptor-{\beta}$. anti-insulin-like growth factor receptor, anti-basic fibroblast growth factor receptor, anti-transforming growth $factor-{\beta}$ receptor and anti-fibronectin receptor were incubated onto the specimens as primary antibodies. After the reaction, FITC-conjugated second antibodies have been applied. When the total numbers of immunoreactive cells and the true positive cells were counted, there were high variability among receptors tested in the present study. The mean number of immunoreactive cells were highest in the case for anti-IFG-1 receptor. However the number of true positive cells were highest in the case for $TGF-{\beta}$ receptor. The present investigation indicated that the receptor for $TGF-{\beta}$ were stongly expressed in the newly forming granulation tissues following the guided tissue regeneration therapy.