• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.165.1-165.1
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• 2003

Transforming growth factor (TGF)-$\beta$, a hormonally active polypeptide found in normal and transformed tissue, is a potent regulator of cell growth and differentiation. In this study, we examined the effect of TGF-$\beta$ on invasion and motility of MCF10A human breast epithelial cells. TGF-$\beta$-induced migration and invasive phenotype of the parental MCF10A cells in a dose-dependent manner. Activity of MMP-2 promoter was increased by TGF-b, suggesting that the TGF-$\beta$-induced invasive phenotype may possibly be mediated by MMP-2 rather than MMP-9. (omitted)

• KSBB Journal
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• 제14권1호
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• pp.9-16
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• 1999

Transforming growth factor $\beta$1(TGF-$\beta$1)은 여러 가지 생물학적 활성을 가지는 관계로 의학적 치료제로서 사용될 가능성이 크다. 본 연구에서는 혈소판추출, 젤여과, 양이온교환 크로마토그래피 및 역상 HPLC등 네 단계의 정제과정으로 이루어져 있는 정제공정을 이용한 TGF-$\beta$1을 값싸고 효울적으로 정제하였다. 이 과정을 거쳐 최종적으로 얻어진 TGF-$\beta$1은 비환원조건하에서 SDS-PAGE를 행한 결과 구매된 TGF-$\beta$1 표준품과 일치한 위치에서 한 개의 band가 관찰되어 순수하다는 것을 확인하였으며 또한 이것이 Westem blot를 통하여 TGF-$\beta$1 항체와 결합하는 것으로부터 TGF-$\beta$1임을 확인하였다 또한, mink lung epithelial cell line 을 이용한 성장저해 실험을 통해 정제된 TGF-$\beta$1이 구매되TGF-$\beta$1 표준품보다 조금 높은 활성을 가지는 것을 확인하였다 최종적으로 농축혈소판 10단위로부터 약 3.7$\mu$g의 정제된 TGF-$\beta$1이 얻어져 그 최종수율은 약 21%였다.

• BMB Reports
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• 제38권1호
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• pp.1-8
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• 2005

Transforming growth factor-$\beta$ is a pleiotropic growth factor that has enthralled many investigators for approximately two decades. In addition to many reports that have clarified the basic mechanism of transforming growth factor-$\beta$ signal transduction, numerous laboratories have published on the clinical implication/application of transforming growth factor-$\beta$. To name a few, dysregulation of transforming growth factor-$\beta$ signaling plays a role in carcinogenesis, autoimmunity, angiogenesis, and wound healing. In this report, we will review these clinical implications of transforming growth factor-$\beta$.

• Journal of Microbiology and Biotechnology
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• 제12권1호
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• pp.121-129
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• 2002

Using recombinant Chinese hamster ovary (CHO) cells, strategies for developing high producers for the recombinant human Transforming Growth $Factor-{\beta}1$ ($TGF-{\beta}1$) protein are proposed and their physiological characteristics in cell cultures were investigated. $TGF-{\beta}1$ is a pleiotrophic polypeptide involved in various biological activities, including cell growth, differentiation, and deposition of extracellular matrix proteins. The CHO cells included human $TGF-{\beta}1$ cDNA in conjunction with a dihydrofolate reductase (DHFR) gene, which was cotransfected into the cells to amplify the transfected $TGF-{\beta}1$ cDNA. As a first-round screening of the transfected cells, a relatively high $TGF-{\beta}1$-producing cell line was selected, and then, it acquired a resistance to increasing concentrations of methotrexate (MTX) up to $60{\mu}M$,resulting in a significant improvement in its $TGF-{\beta}1$ biosynthetic ability. After applying a monoclonal selection strategy to the MTX-resistant cells, more productive cells were screened, including the APP-3, App-5, and App-8 cell lines. These high producers were compared with two other cell lines (AP-l cell line without amplification of transfected $TGF-{\beta}1$ cDNA and nontransfectant of $TGF-{\beta}1$ cDNA) in terms of cell growth, $TGF-{\beta}1$ productivity, sugar uptake, and byproduct formation, in the presence or absence of MTX in the culture medium. Consequently, both monoclonal selection as well as an investigation of the physiological characteristics were found to be needed for the efficient screening of higher $TGF-{\beta}1$ producers, even after the transfection and amplification of the transfected gene.

• BMB Reports
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• 제41권10호
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• pp.728-732
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• 2008

FoxO3a is a member of the forkhead box class O (FoxO) transcription factor family and an important regulator of apoptosis. This work aimed to elucidate the involvement of FoxO3a in transforming growth factor-${\beta}1$(TGF-${\beta}1$)-induced apoptosis in FaO rat hepatoma cells. TGF-${\beta}1$ caused a time-dependent activation of FoxO3a and a subsequent increase in FoxO response-element-containing luciferase reporter activity, which was Akt-sensitive. The FaO cells stably transfected with a wild type FoxO3a were more susceptible to the formation of apoptotic bodies, populations of sub-G1 apoptotic cells, and collapse of the mitochondrial-membrane potential triggered by TGF-${\beta}1$. In contrast, transfection with small-interfering RNA (siRNA) oligonucleotide specific for FoxO3a significantly inhibited caspase activation in FaO cells treated with TGF-${\beta}1$. It thus appears that FoxO3a plays a crucial mediatory role in the TGF-${\beta}1$ signaling pathway leading to apoptosis.

• 생명과학회지
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• 제22권11호
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• pp.1500-1506
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• 2012

Transforming growth factor-${\beta}$ (TGF-${\beta}$)에 의해 유도되는 세포사멸 과정은 간에서 손상 받은 조직이나 비정상적인 조직을 제거하는데 중요한 역할을 담당한다. 간세포에서 TGF-${\beta}$에 의해 유도되는 세포사멸 과정 동안 중요한 기능을 담당하는 유전자를 탐색하고자 쥐의 간세포인 AML12 세포를 이용하여 TGF-${\beta}$ 처리 전후에 발현이 변화되는 유전자를 microarray analysis를 통해 확인하였다. TGF-${\beta}$에 의해 여러 가지 유전자들의 발현이 변화됨을 확인하였는데, 그 가운데 여러 가지 세포사멸 인자들의 활성을 억제하여 세포사멸을 억제한다고 알려져 있는 SGK1의 발현 감소를 확인하였다. TGF-${\beta}$에 의해 SGK1의 mRNA와 단백질 level이 모두 감소함을 확인하였고, 항상 active한 형태의 SGK1 (CA-SGK1)을 발현시켰을 때 TGF-${\beta}$에 의한 세포사멸이 억제됨을 확인하였다. 이러한 결과들은 간세포에서 SGK1의 발현 감소가 TGF-${\beta}$에 의한 세포사멸을 유도하는데 중요한 기능을 담당할 가능성이 높음을 의미하는 것이다.

• IMMUNE NETWORK
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• 제1권3호
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• pp.244-249
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• 2001

The transforming growth $factor-{\beta}$ ($TGF-{\beta}$) is a multifunctional cytokine modulating the onset and course of autoimmune disease as shown in experimental models. In synovial inflammation, there is a potential role for $TGF-{\beta}$ in repairment, the inhibition of cartilage and bone destruction, and the down-regulation of immune response. The biologic effects of $TGF-{\beta}$ depend on the cell type, the isoform and the availability of active $TGF-{\beta}$. We investigated $TGF-{\beta}$ expression in patients with rheumatoid arthritis (RA) and compared to those of osteoarthritis (OA). And we determined a correlation between $TGF-{\beta}1$ and $TGF-{\beta}2$, and also the relationships between each $TGF-{\beta}$ isoform and the parameters for disease activity of RA. Methods: The study population consisted of 20 patients with RA and 20 patients with OA. The commercial ELISA kit was used to study $TGF-{\beta}1$ and $TGF-{\beta}2$ levels in peripheral blood (PB) and synovial fluids (SF). Results: 1) While PB $TGF-{\beta}1$ level was of no difference between RA and OA patient groups, SF $TGF-{\beta}1$ level was higher in RA group than OA group. Similarly, PB $TGF-{\beta}2$ levels of RA and OA groups was not different, but SF $TGF-{\beta}2$ levels was higher in RA group than OA group. 2) In patients with RA, the $TGF-{\beta}1$ levels were higher than $TGF-{\beta}2$ in both the PB and SF, while in patients with OA, there showed higher readings for $TGF-{\beta}1$ than $TGF-{\beta}2$ in SF but no difference between $TGF-{\beta}1$ and $TGF-{\beta}2$ levels in PB. 3) In patients with RA, there were no correlations between PB $TGF-{\beta}1$ and PB $TGF-{\beta}2$ levels, nor between SF $TGF-{\beta}1$ and SF $TGF-{\beta}2$ levels. At the same way, there was no correlation between PB $TGF-{\beta}1$ and SF $TGF-{\beta}1$ levels, nor between each levels of $TGF-{\beta}2$ in patients with RA. 4) There was also no correlation between each $TGF-{\beta}$ isoform and the parameters for disease activity such as ESR, CRP, tender joint count, swollen joint count, rheumatoid factor, and the duration of morning stiffness except between in PB $TGF-{\beta}1$ and disease duration of RA (r=0.637, p<0.01). Conclusion: Each $TGF-{\beta}$ isoforms were higher in synovial fluid of patients with RA than that of patients with OA. The data from the RA patients demonstrated different patterns of expressions of the isoforms depending on which compartment (PB or SF) was investigated. The quantification of different $TGF-{\beta}$ isoform is thought to be important when $TGF-{\beta}$ is measured under disease conditions of RA.

• Clinical and Experimental Reproductive Medicine
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• 제38권4호
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• pp.210-215
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• 2011

Objective: This study was performed to identify whether growth and differentiation factor-9 (GDF-9) and transforming growth factor-${\beta}1$ (TGF-${\beta}1$) expressions would be lower in the follicular fluid (FF) of those over age 35 who underwent IVF than under age 35. Methods: A total of 24 IVF cycles (20 patients) were included in this study. All of patients were stimulated for IVF by the GnRH short protocol and divided into two groups for analysis, according to their age: <35 group (14 cycles, 11 patients) vs. ${\geq}35$ group (10 cycles, 9 patients). The expression levels of GDF-9 and TGF-${\beta}1$ were determined by western blotting and quantitative enzyme-linked immunosorbent assay. Results: The numbers of retrieved oocytes and metaphase II oocytes were significantly lower in the ${\geq}35$ group. Lower expression of GDF-9 and TGF-${\beta}1$ by western blotting in the ${\geq}35$ group were observed as well. The mean GDF-9 and TGF-${\beta}1$ levels by enzyme-linked immunosorbent assay were lower in the ${\geq}35$ group. The values were $6,850.5{\pm}928.4$ ng/L vs. $3,333.3{\pm}1,089.2$ ng/L of GDF-9 ($p$ <0.05) and $3,844.1{\pm}571.1$ ng/L vs. $2,187.7{\pm}754.0$ ng/L of TGF-${\beta}1$ ($p$ <0.05). A negative correlation between GDF-9 and age was observed (r=-0.546, $p$=0.006). Conclusion: GDF-9 and TGF-${\beta}1$ production from stimulated ovaries during IVF appears to decrease with age.

• 대한두경부종양학회지
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• 제18권2호
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• pp.135-141
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• 2002

Backgrounds and Objectives: Metastasis is a complex multistep process that requires sequential interactions between the invasive cell and the extra-cellular matrix. Transforming growth factor-${\beta}1$ ($TGF-{\beta}1$) is a multifunctional regulator of cellular differentiation, motility and growth. Loss of sensitivity to the growth inhibitory effects by $TGF-{\beta}1$ plays important roles in neoplastic progression. The aim of this study was to investigate the role of $TGF-{\beta}1$ in the neoplastic invasion and metastasis through matrix metalloproteinase (MMP) of laryngeal cancer cell lines. Material and Methods: Two laryngeal cancer cell lines, SNU-899 and SNU-1076 were treated with recombinant $TGF-{\beta}1$, and the expression of MMP-2 and MMP-9 was immunohistochemically evaluated and gelatinase activity was studied by gelatin zymogram. Results: The cell growth inhibition was evident on 4th days after 1ng/ml and 10ng/ml $TGF-{\beta}1$ treatment. The expressions of MMP-2 and MMP-9, and their gelatinase activities were increased in dose-dependent manner. Conclusion: $TGF-{\beta}1$ treatment in laryngeal cancer cell lines induces the expression of MMP-2 and MMP-9, thus playing a role in the digestion of extracellular matrix gelatin.

• 생물정신의학
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• 제13권1호
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• pp.32-37
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• 2006

Background : Several studies have suggested that alterations of cytokine level could be related to the pathophysiology of bipolar disorder. In this study, we measured plasma level of Interleukin-12(IL-12), a pro-inflammatory cytokine and transforming growth factor-${\beta}$1(TGF-${\beta}$1), an anti-inflammatory cytokine before and after treatment in acute manic patients. Methods : The plasma concentrations of IL-12 and TGF-${\beta}$1 were measured using quantitative ELISA in 18 bipolar disorder patients and 25 normal controls at admission and 6 weeks later. The psychopathology was measured by Brief Psychiatric Rating Scale(BPRS) and Young Mania Rating Scale(YMRS). Results : IL-12 levels were significantly higher in bipolar manic patients than in controls before treatment. Following the 6-week treatment, the IL-12 level was decreased than before treatment, but sustained still higher level than normal control. TGF-${\beta}$1 level was not significant different between manic patients and normal controls before treatment, but was increased after treatment comparing with before treatment in bipolar patients. The ratio of IL-12 and TGF-${\beta}$1 was significantly decreased after treatment. Conclusion : Cytokine abnormalities in bipolar disorder might be involved in the pathophysiology of the illness. It is possible that TGF-${\beta}$1 plays an important role in the regulation of immunological imbalance in bipolar disorder.