• 대한구순구개열학회지
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• 제4권1호
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• pp.13-26
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• 2001

Cleft lip and/or palate is the congenital orofacial malformation most commonly occurred in humans, The disease is multifactorial and is probably caused by genetic and/or environmental factors, So, there are many problems in research concerning etiology and in treatment of the disease, Even the most practiced and sophisticated methods of surgical repair are necessarily followed by scar contraction and fibrosis, which result in skeletal defects, dental abnormalities, cosmetic disfigurement, and speech impairment, As a result, Fetal surgery can be considered but practiced rarely when the deformity is not fatal to life, And treatment of cleft palate is performed in the form of medicine projection into uterus in animal experiments, Many studies show that growth factor and its receptor emerge from the developing palate; and the epidermal growth factor receptors have a important role in craniofacial development and in palatal fusion, The palatal morphogenesis of the avine is different from the mammal's; it takes the form of physiologic cleft palate, Recently, cleft palate fusion experiment was performed when the avine were in the period of palate formation through the exogenous TGF-β3 addition, and it showed that the exogenous TGF-β3 makes fusion of divided palate through certain process when cleft palate is occurred in palatal formation, In this study, I had the conformation of the fusion of cleft palate through the addition of TGF-β in case of chicken embryo, and observed the effect of TGF-β in EGF receptor distribution, And the following is the results of this study, 1. In case of the TGF-βl and β3 addition group, there was the decrease of EGFR(Epidermal Growth Factor Receptor) immunoreactivity in mesenchymal cells beneath the medial edge epithelium and also in epithelial mesenchymal interface which is between medial edge epithelium and nasal septum in 72 hours, 2, The immunoreactivity of the control group resembles that of normal chicken embryo palate in development, 3. In the view through fluorescence confocal microscopy, there was confluence in TGF-β3 addition group, This shows that the confluence induced by exogenous TGF-β3 is related to EGFR expression in palate of chicken embryo, which is a physiologic cleft palate model.

• Tuberculosis and Respiratory Diseases
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• 제70권3호
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• pp.206-217
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• 2011

Background: Transcription factor FOXP3 characterizes the thymically derived regulatory T cells. FOXP3 is expressed by cancer cell itself and FOXP3 expression was induced by TGF-${\beta}$ treatment in pancreatic cancer cell line. However, the expression of FOXP3 expression is not well known in patients with lung cancer. This study was conducted to investigate the expression of FOXP3 in patients with lung cancer and to investigate the regulation of FOXP3 expression by the treatment of TGF-${\beta}$ and DNA methyltransferase inhibitor in lung cancer cell lines. Methods: FOXP3 expression in the tissue of patients with resected non-small cell lung cancer (NSCLC) was evaluated by immunohistochemistry. The regulation of FOXP3 expression was investigated by Western blot and RT-PCR after lung cancer cell lines were stimulated with TGF-${\beta}1$ and TGF-${\beta}2$. The regulation of FOXP3 expression was also investigated by RT-PCR and flow cytometry after lung cancer cell lines were treated with DNA methyltransferase inhibitor (5-AZA-dC). Results: FOXP3 expression was confirmed in 27% of patients with NSCLC. In NCI-H460 cell line, TGF-${\beta}2$ decreased FOXP3 mRNA and protein expressions. In A549 cell line, both TGF-${\beta}1$ and TGF-${\beta}2$ decreased FOXP3 mRNA and protein expressions. 5-AZA-dC increased FOXP3 mRNA expression in NCI-H460 and A549 cell lines. Moreover, 5-AZA-dC increased intracellular FOXP3 protein expression in A549 cell lines. Conclusion: It was shown that FOXP3 is expressed by cancer cell itself in patients with NSCLC. Treatment of TGF-${\beta}2$ and DNA methyltransferase inhibitor seems to be associated with the regulation of FOXP3 expression in lung cancer cell lines.

• 한국융합학회논문지
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• 제9권5호
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• pp.91-97
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• 2018

본 연구는 25% 에탄올에 손상된 간조직에서 $TGF-{\beta}_1$와 c-Myc, Erb-B2, $Thymosin-{\beta}_4$ 유전자의 발현을 알아 보고자 실시 하였다. 실험군은 2군으로 나누어 25% 에탄올로 간 손상을 유발한 실험군과 정제수를 투여한 대조군으로 나누어 실험하였다. 검사 결과는 25% 에탄올를 투여 했던 실험군은 대조군에 비하여 $TGF-{\beta}_1$, c-Myc 및 $Thymosin-{\beta}_4$ 유전자의 발현 증가를 알 수 있었으며 Erb-B2 유전자는 뚜렷한 발현을 알 수 없었다. 또한 손상된 간 조직에서 헤마톡실린 에오진 염색을 통한 세포 손상을 관찰 할 수 있었다. 결론적으로 기존 임상에서 간 기능 관련 질병 예방과 질환 판정 시 혈청학적, 조직학적 검사 외에 $TGF-{\beta}_1$, c-Myc 및 $Thymosin-{\beta}_4$의 분자 진단 기법에 의한 유전자 발현 상태를 융합 검사함으로써 간 질환 판정의 보조 자료로 활용 될 수 있을 것으로 사료 된다.

• Biomolecules & Therapeutics
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• 제24권2호
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• pp.132-139
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• 2016

The endothelial-mesenchymal transition (EndMT) is known to be involved in the transformation of vascular endothelial cells to mesenchymal cells. EndMT has been confirmed that occur in various pathologic conditions. Transforming growth factor ${\beta}1$ (TGF-${\beta}1$) is a potent stimulator of the vascular endothelial to mesenchymal transition (EMT). Aspirin-triggered resolvin D1 (AT-RvD1) has been known to be involved in the resolution of inflammation, but whether it has effects on TGF-${\beta}1$-induced EndMT is not yet clear. Therefore, we investigated the effects of AT-RvD1 on the EndMT of human umbilical vein vascular endothelial cells line (HUVECs). Treatment with TGF-${\beta}1$ reduced the expression of Nrf2 and enhanced the level of F-actin, which is associated with paracellular permeability. The expression of endothelial marker VE-cadherin in HUVEC cells was reduced, and the expression of mesenchymal marker vimentin was enhanced. AT-RvD1 restored the expression of Nrf2 and vimentin and enhanced the expression of VE-cadherin. AT-RvD1 did also affect the migration of HUVEC cells. Inhibitory ${\kappa}B$ kinase 16 (IKK 16), which is known to inhibit the NF-${\kappa}B$ pathway, had an ability to increase the expression of Nrf2 and was associated with the inhibition effect of AT-RvD1 on TGF-${\beta}1$-induced EndMT, but it had no effect on TGF-${\beta}1$-induced EndMT alone. Smad7, which is a key regulator of TGF-${\beta}$/Smads signaling by negative feedback loops, was significantly increased with the treatment of AT-RvD1. These results suggest the possibility that AT-RvD1 suppresses the TGF-${\beta}1$-induced EndMT through increasing the expression of Smad7 and is closely related to oxidative stress.

• 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.

• 대한치과교정학회지
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• 제30권6호
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• pp.713-721
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• 2000

골세포는 골대사에 영향을 미치는 다양한 성장인자와 싸이토카인을 생성하여 골 기질로 유리시킨다. 이 연구는 쥐의 장골 세포 배양 모델에서 recombinant human IL-$1\beta$가 $PGE_2$ 합성과 plasminogen activator의 활성 조절을 통한 골 흡수 유도 기전의 일단을 구명하고, 이와 동시에 TGF-$\beta$에 의한 골흡수 억제 기전을 해명하는데 그 목적이 있다. 쥐의 장골 세포를 배양하여 통법의 골모세포 phenotype을 발현하는 세포를 분리하고 세포 배양능, alkaline phosphatase assay, PG assay, 골흡수능 측정들을 시행하여 다음의 결과를 얻었다. 1. IL-$1\beta$는 쥐의 골모세포의 증식, $PGE_2$ 생성 및 palsmonogen activator의 활성을 촉진하였다. 2. IL-$1\beta$는 쥐의 골모세포에서의 alkaline phosphatase 활성을 감소시켰다. 3. rhIL-$1\beta$는 골 흡수를 촉진시켰다. 4. TGF-$\beta$는 쥐의 장골 세포에서 골의 흡수를 억제하였으며, Vitamin $D_3$에 의하여 유도된 골 흡수를 억제하였다. 이상의 연구 결과는 IL-$1\beta$에 의한 골 파괴의 병인과 관련하여 골 세포 대사의 병리학적 조절에 있어서의 IL-$1\beta$의 역할을 지지하며, 이와 동시에 골 흡수 억제에 있어서의 TGF-$\beta$의 역할을 확인시켜주는 것으로 생각된다.

• Journal of Chest Surgery
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• 제36권2호
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• pp.86-90
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• 2003

폐 형성에 활성적인 또는 억제적인 기능을 갖고 있다고 알려져 있는 FGF-7 성장인자, BMP수용체 II, 그리고 TGF-$\beta$ 수용체 II 유전자의 비정상 발현이 폐기포 생성에 관여하는지를 각각의 단일성 클론 항체를 사용하여 수술로 절제된 자연기흉 환자의 폐기포 조직들을 면역조직염색 방법으로 염색하여 관찰하였다. 대상 및 방법: 재발성 또는 지속성 기흉으로 흉강경 또는 개흉술로 폐기포 절제술을 실시한 환자들을 대상으로 하였다. 총 31명의 환자로 15세에서 39세까지 연령분포를 보였으며 남자 30명, 여자 1명이었다. 폐기포 절제는 비디오흉강경이나 소절개개흠술을 통하여 폐기포벽에 손상을 가하지 않게 주의하면서 비디오흉강경용 스태플러(Endo GIA stapler)를 이용하여 절제하였으며 가능한 원형을 유지하여 신선한 상태로 포르마린에 고정하여 면역조직화학적 연구를 위한 표본을 만들었다. 폐기포 조직 슬라이드를 단일클론성 항 TGF-$\beta$ 수용체 II, BMP수용체 II 그리고 FGF-7인자 항체를 이용하여 면역조직학적 염색방법으로 관찰하였다. 결과: 전체 환자 31명중 TGF-$\beta$ 수용체 II항체에 양성 반응을 나타낸 환자수는 모두 24명이었다. 이들 중에는 18명이 강한 양성 반응을 보였고, 6명이 약한 양성 반응을 보였다 면역조직화학적 염색 결과를 고배율 현미경으로 살펴보면, TGF-$\beta$ 수용체 II의 염색이 기흉과 정상 폐조직 경계 부위에서 측히 강하게 염색됨이 관찰되었다. 이에 반하여, BMP수용체 II 그리고 FGF-7인자의 항체를 이용한 면역조직학적 염색 결과는 모든 환자의 조직들에서 음성으로 관찰되었다. 결론: 폐 조직이 형성될 때, 억제유전자의 역할을 담당하고 있다고 알려진 TGF-$\beta$ 수용체 II의 발현이 증가되면서 폐기포가 생성될 수 있다는 가능성을 제시하였다. 이번 결론은 면역조직학적 염색 실험 결과만으로 밝혀진 사실임으로 좀 더 체계적인 분자생물학적 인 연구가 요구된다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권1호
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• pp.8-18
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• 2006

Purpose: The purpose of this study was to verify that the expressions of angiogenin, transforming growth factor-beta(TGF-${\beta}$), vascular endothelial growth factor(VEGF), human apurinic/apyrimidinic endonuclease(APEX) and tumor necrosis factor-alpha(TNF-${\alpha}$) were associated with the tumorigenesis of the oral squamous cell carcinoma(OSCC). Materials and Methods: Fifty-one samples of OSCC and fifteen normal oral mucosae were obtained to analyze the expression levels of above five factors. mRNA expressions were quantified by the quantitative competitive PCR(QC-PCR) method. After 2% agarose gel electrophoresis stained with ethidium bromide, the concentration of mRNA was calculated by a digital image analysis system. The expression levels of angiogenin, TGF-${\beta}$, VEGF, APEX and TNF-${\alpha}$ were compared by unpaired Student's t-tests between cancer and normal tissues. We analyzed statistically to find the cut-off values that would be useful as diagnostic markers, and the linear regression analysis between every two factors of these five factors by SAS system. Results: All of these five factors (angiogenin: P<0.0037, TGF-${\beta}$: P<0.0001, VEGF: P<0.0102, APEX: P<0.0023, TNF-${\alpha}$: P<0.0074) were significantly correlated with OSCC. In the analysis to find the cut-off values for the diagnosis, we could not find any value that had a reasonable sensitivity and specificity. In the linear regression analysis, there were correlations between angiogenin and TNF-${\alpha}$, TGF-${\beta}$ and VEGF, TGF-${\beta}$ and APEX, TGF-${\beta}$ and TNF-${\alpha}$, VEGF and APEX, VEGF and TNF-${\alpha}$, APEX and TNF-${\alpha}$. Conclusion: Our results suggest that not only angiogenin, TGF-${\beta}$, VEGF, APEX and TNF-${\alpha}$ are significantly associated with the tumorigenesis, but also the close relationship between these factors might enhance the tumorigenesis of OSCC. We can not find clinical availability for diagnosis.

• Asian-Australasian Journal of Animal Sciences
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• 제32권4호
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• pp.477-484
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• 2019

Objective: We aimed to observe hair follicle (HF) development in the dorsal skin and elucidate the expression patterns of genes and proteins related to skin and HF development in Rex rabbits from birth to 8 weeks of age. Methods: Whole-skin samples were obtained from the backs of Rex rabbits at 0, 2, 4, 6, and 8 weeks of age, the morphological development of primary and secondary HFs was observed, and the gene transcript levels of insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), bone morphogenetic protein 2 (BMP2), transforming growth factor ${\beta}-1$, 2, and 3 ($TGF{\beta}-1$, $TGF{\beta}-2$, and $TGF{\beta}-3$) were examined using quantitative real-time polymerase chain reaction (PCR). Additionally, Wnt family member 10b (Wnt10b) and ${\beta}$-Catenin gene and protein expression were examined by quantitative real-time PCR and western blot, respectively. Results: The results showed significant changes in the differentiation of primary and secondary HFs in Rex rabbits during their first 8 weeks of life. The IGF-I, EGF, $TGF{\beta}-2$, and $TGF{\beta}-3$ transcript levels in the rabbits were significantly lower at 2 weeks of age than at birth and gradually increased thereafter, while the BMP2 and $TGF{\beta}-1$ transcript levels at 2 weeks of age were significantly higher than those at birth and gradually decreased thereafter. ${\beta}$-Catenin gene expression was also significantly affected by age, while the Wnt10b transcript level was not. However, the Wnt10b and ${\beta}$-catenin protein expression levels were the lowest at 2 and 4 weeks of age. Conclusion: Our data showed that a series of changes in HFs in dorsal skin occurred during the first 8 weeks. Many genes, such as IGF-I, EGF, BMP2, $TGF{\beta}-1$, $TGF{\beta}-2$, $TGF{\beta}-3$, and ${\beta}$-Catenin, participated in this process, and the related proteins Wnt10b and ${\beta}$-Catenin in skin were also affected by age.

• IMMUNE NETWORK
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• 제14권1호
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• pp.30-37
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• 2014

Collaboration of TLR and non-TLR pathways in innate immune cells, which acts in concert for the induction of inflammatory cytokines, can mount a specific adaptive immune response tailored to a pathogen. Here, we show that murine DC produced increased IL-23 and IL-6 when they were treated with LPS together with curdlan that activates TLR4 and dectin-1, respectively. We also found that the induction of the inflammatory cytokine production by LPS and curdlan requires activation of IKK. However, the same treatment did not induce DC to produce a sufficient amount of TGF-${\beta}$. As a result, the conditioned media from DC treated with LPS and curdlan was not able to direct $CD4^+$ T cells to Th17 cells. Addition of TGF-${\beta}$ but not IL-6 or IL-$1{\beta}$ was able to promote IL-17 production from $CD4^+$ T cells. Our results showed that although signaling mediated by LPS together with curdlan is a potent stimulator of DC to secrete many pro-inflammatory cytokines, TGF-${\beta}$ production is a limiting factor for promoting Th17 immunity.