• 미생물학회지
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• 제35권2호
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• pp.164-168
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• 1999

TGF-$\beta$1은 LPS 로 자극시킨 마우스의 spleen B cell 의 IgA와 IgG2b의 항체 합성을 선택적으로 증가시킨다고 알려져있다. 본 연구에서는 TGF-$\beta$1과 80%의 아미노산을 공유하는 TGF-$\beta$3가 마우스 spleen B cell 과 mesenteric lymph node B cell의 항체 합성에 미치는 영향을 IL-5와 함께 조사하였다. LPS로 활성화된 spleen B cell 에 TGF-$\beta$3만을 처리한 조건에서 IgA 항체합성이 약간 증가하였고, IL-5와 함께 넣어 준 배양조건에서는 IgA 항체가 현격히 증가하였다 IgG2b 합성의 증가는 TGF-$\beta$3 자극만으로도 가능하였고 IgA 와는 달리 IL-5 의 첨가 효과는 관찰되지 않았다. 한편, TGF-$\beta$3는 IgM 과 IgG1 항체 합성을 감소시켰고, IL-5와 함께 존재한 경우에도 의미있는 합성 증가는 볼 수 없었다. ELISPOT assay로 IgA 합성 세포수의 변화를 조사해본 결과, TGF-$\beta$3 단독으로도 IgA 합성세포수를 증가시켰으며, 이때 IL-5가 존재하였을 때 세포수가 조금 더 증가하였다. 이상의 결과는 TGF-$\beta$3가 약간의 차이는 있지만 TGF-$\beta$1과 유사하게 항체합성 패턴에 영향을 미침을 보여준다. 마지막으로, TGF-$\beta$3과 IL-5에 대한 MLN B cell 의 IgA와 IgG2b 항체합성 패턴은 spleen B cell 과 비슷하였다. 그러나 MLN B cell 의 IgG1 항체 합성은 spleen B cell과는 달리 TGF-$\beta$3에 의해 증가하였다. 본 실험의 결과는 전반적으로 TGF-$\beta$3가 TGF-$\beta$1과 비슷한 정도로 마우스 B cell의 항체합성에 영향을 미침을 보여준다. 그렇지만, 생체 내에서TGF-$\beta$3의 발현조절이 TGF-$\beta$1과 다를 것으로 예상됨으로 과연 TGF-$\beta$3가 B cell 분화에서 중요한 조절인자로 작용할지는 좀 더 연구되어야 할 것이다.

• Toxicological Research
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• 제23권3호
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• pp.197-205
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• 2007

Cancer metastasis is a major determinant of cancer patient mortality. Mounting evidence favors a strong positive role for $TGF-{\beta}$ in human cancer progression. The complex pattern on cross-talk of $TGF-{\beta}$ and the related other signaling pathways is an important area of investigation that will ultimately contribute to understanding of the bifunctional role of $TGF-{\beta}$ in cancer progression. This review summarizes some of the current understanding of $TGF-{\beta}$ signaling with a major focus in its contribution to the tumor cell invasion and metastasis. Five issues are addressed in this review: (1) $TGF-{\beta}$ signaling, (2) $TGF-{\beta}$ and EMT, (3) $TGF-{\beta}$ and MMP, (4) $TGF-{\beta}$ and Ras, and (5) Role of $TGF-{\beta}$ in invasion and metastasis. Due to the bifunctional cellular effects of $TGF-{\beta}$, as a tumor promoter and a tumor suppressor, more precisely defined $TGF-{\beta}$ signaling pathways need to be elucidated. According to the current literature, $TGF-{\beta}$ is clearly a major factor stimulating tumor progression through a complex spectrum of the interplay and cross-talk between various signaling molecules. Understanding the role of $TGF-{\beta}$ in invasion and metastasis will provide valuable information on establishing strategies to manipulate $TGF-{\beta}$ signaling which should be a high priority for the development of anti-metastatic therapeutics.

• Animal cells and systems
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• 제4권3호
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• pp.273-278
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• 2000

Transforming growth factor-$\beta$ (IGF-$\beta$)s are multifunctional small polypeptides synthesized in most cell types. TGF-$\beta$ exerts pivotal effects on both bone formation and resorption. In addition, increasing lines of evidence implicate TGF-$\beta$ as a potential coupling factor between these two processes during bone remodeling. In the present study, the expression form and the activation mechanism of latent-TGF-$\beta$ were investigated using specific antibodies for each isoform. TGF-$\beta$s were observed to be synthesized and accumulated in a large amount in cultured osteoblastic cells. The estimated molecular weights of intracellular TGF-$\beta$2 and -$\beta$3 were 49 and 55 kDa, respectively. Based on proteolytic digestion study and immunofluorescence observation, these precursor forms seemed to be accumulated in distinct intracellular compartments. To examine whether the internal pool of TGF-$\beta$ was possiblely regulated by external signals, their biological activites were examined in a conditioned media of this cell. Although the intact conditioned media did not contain detectable TGF-$\beta$ activity, heat-treatment or acid-activation of the conditioned media revealed significant TGF-$\beta$ activity. Furthermore, in the presence of estrogen, this activity was dramatically diminished. It is known that activation of latent TGF-$\beta$ can be achieved by different chemical and enzymatic treatments, or by incubation with certain cell types. This extracellular activation was suggested as a key step in the regulation of TGF-$\beta$ activity. In addition to these extracellular activation, this study suggests that the synthesis and intracellular processing are important regulation steps for TGF-$\beta$ action. In addition, this regulation Is specific for TGF-$\beta$ type 2, because the change was not observed in TGF-$\beta$3 in osteoblastic cell line.

• 생명과학회지
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• 제18권4호
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• pp.461-466
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• 2008

Transforming growth $factor-{\beta}$ ($TGF-{\beta}$)에 의해 유도되는 세포사멸 과정은 정상 조직에서 손상 받은 조직이나 비정상 적인 조직을 제거하는데 중요한 역할을 담당한다. Gadd45b는 p38 kinase를 활성화시킴으로 $TGF-{\beta}$에 의해 유도되는 세포사멸 과정을 매개한다고 알려져 있다. 본 연구에서는 $TGF-{\beta}$에 의해 세포사멸이 일어나는 EpH4 세포에서 Gadd45b 유전자의 발현이 $TGF-{\beta}$에 의해 촉진됨을 보여주었다. 어떠한 기작으로 $TGF-{\beta}$에 의해 Gadd45b 유전자의 발현이 촉진되는지 알아보기 위해 Gadd45g 유전자의 5'-flanking region을 cloning하였으며, EpH4 세포에서 $TGF-{\beta}$에 의해 그 promoter activity가 증가함을 확인하였다. 여러 가지 deletion mutants를 제조하여 promoter activity를 조사한 결과 전사 개시점으로부터 220 bp upstream 부위 에 promoter activity에 필수적인 sequence가 존재함을 확인하였다. 또한 $TGF-{\beta}$에 의한 Gadd45b 유전자의 promoter activity에 Smad2, Smad3, 그리고 Smad4가 중요한 기능을 담당함도 확인하였다. 마지막으로 ras 유전자가 도입되어 $TGF-{\beta}$에 의한 세포사멸이 억제되어있는 EpRas 세포에서 $TGF-{\beta}$에 의한 Gadd45b 유전자의 발현을 확인한 결과 EpRas 세포에서 $TGF-{\beta}$에 의한 Gadd45b 유전자의 발현이 억제됨을 확인하였다. 이러한 결과는 Gadd45b 유전자가 EpH4 세포에서 $TGF-{\beta}$에 의한 세포사멸을 유도하는데 중요한 기능을 담당할 가능성이 높음을 의미하는 것이다.

• 대한한의학회지
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• 제24권2호
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• pp.1-11
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• 2003

Objectives : The aim of this study was to characterize the effect of Injinchunggan-tang on $TGF-{\beta}1-induced$ hepatic fibrosis. Methods : mRNA and protein expression levels of $TGF-{\beta}1$ in Injinchunggan-tang-treated HepG2 cells were compared to untreated cells using quantitative RT-PCR and ELISA assay, respectively. mRNA expression levels of the TGF-1 pathway genes (TR-1, TR-II, Smad2, Smad3, Smad4, and PAI-1) and fibrosis-associated genes (CTGF, fibronectin, and collagen type 1) were evaluated by quantitative RT-PCR. The effect of Injinchunggan-tang on cell proliferation of T3891 human fibroblast was evaluated using [$^3H$]thymidine incorporation assay. Results : Expression of $TGF-{\beta}1$ mRNA and protein was inhibited by Injinchunggan-tang in a dose- and time-dependent manner. Whereas $TGF-{\beta}1-mediated$ induction of PAI-1 was suppressed by Injinchunggan-tang, expression of the $TGF-{\beta}1$ pathway genes such as TR-1, TR-II, Smad2, Smad3, and Smad4 was not affected by Injinchunggan-tang treatment. Injinchunggan-tang was found to inhibit $TGF-{\beta}1-induced$ cell proliferation of T3891 human fibroblast, and also abrogated $TGF-{\beta}1-mediated$ transcriptional up-regulation of CTGF, fibronectin, and collagen type I. Conclusions : This study strongly suggests that the liver cirrhosis-suppressive activity of Injinchunggan-tang may be derived at least in part from its inhibitory effect on $TGF-{\beta}1$ functions, such as blockade of $TGF-{\beta}1$ stimulation of fibroblast cell proliferation and fibrosis-related gene expression as well as expression of $TGF-{\beta}1$ itself.

• 대한의생명과학회지
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• 제5권2호
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• pp.181-190
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• 1999

한국인의 대표적인 성인 고형 종양인 위암, 간암, 유방암과 소아 백혈병 및 2종의 소아 고형 종양 환자로부터 혈장 transforming growth factor-$\beta$1 (TGF-$\beta$1) 농도를 sandwich ELISA 분석법을 이용해 측정함으로써 TGF-$\beta$1을 이 질환들에 대한 새로운 종양표지자 (tumor marker)로 사용할 수 있는지 검토하였다. 토한 연령 및 성별에 따른 혈장 TGF-$\beta$1 농도의 정상치를 조사하였다. 신생아에서 70대까지 혈장 TGF-$\beta$1 농도의 차이는 없었고 남녀간의 차이도 없었다. 위암 환자의 혈장 TGF-$\beta$1 농도는 16.0$\pm$6.8 ng/ml (평균$\pm$표준편차)로 정상 대조군의 TGF-$\beta$1 농도 (8.3$\pm$5.0 ng/ml) 보다 유의하게 높았으나 간암, 유방암 환자의 혈장 TGF-$\beta$1 농도는 대조군과 차이가 없었다. 그리고 위암 환자 16명 ,간암 환자 8명, 유방암 환자 7명 중 각각 7명 (43.7%), 1명 (12.5%), 1명 (14.3%)에서만 혈장 TGF-$\beta$1 농도가 증가되었다. 5명의 소아 백혈병 환자에서는 관해 (remission)여부와 상관없이 혈장TGF-$\beta$1농도가 모두 정상 범위에 있었으나 2명의 소아 고형암 환자에서는 종양 절제 전에는 혈장 TGF-$\beta$1농도가 높았다가 절제 후 정상으로 떨어졌다. 결론적으로 1)정상인의 혈장 TGF-$\beta$1 농도는 연령 및 성별에 따른 차이가 없다는 것을 알 수 있었고, 2)성인 고형암인 위암, 간암, 유방암에서는 낮은 민감도로 인해 TGF-$\beta$1을 진단을 위한 선별 검사로 이용하기에는 부적절한 것으로 판단되었으며, 3)정상 대조군보다 혈장 TGF-$\beta$1 농도가 높았던 위 암 환자와 종양 절제 전후로 혈장 TGF-$\beta$1 농도가 민감하게 변했던 소아 고형암 환자에 대 해서는 향후 표본 수를 늘려 부가적인 연구를 해야 할 것으로 사료된다.

• The Journal of Korean Physical Therapy
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• 제14권3호
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• pp.145-173
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• 2002

This study was performed to investigate the effect of ultrasound irradiation on $TGF-\beta_1$ expression in the surgically injured achilles tendons of rats. The results of this study were as following: 1. The control group (3 days after injury) expressed little immunoreactivity for $TGF-\beta_1$. 2. In the experimental groups, $TGF-\beta_1$ immunoreactivity of group 11(applied US for 3 days) was increased markedly than that of group 1(applied US for 1 day). 3, The experimental group 11(applied US for 3 days) expressed higher immunoreactivity for $TGF-\beta_1$ than control group. These findings suggest that ultrasound irradiation on the injured Achilles tendon may be of benefit such as increasing $TGF-\beta$ release in the inflammatory phase of heal ins process.

• 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.

• 한국임상수의학회지
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• 제11권1호
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• pp.389-392
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• 1994

To purify transforming growth factor type beta(TGF-$\beta$) in canine platelets, Sephadex G-75 gel filtration and semipreparative HPLC were carried out. The column of $2.0 {\times}120cm$ was used for gel filtration and one inch semipreparative column filled with SP-Toyopeal for HPLC. Electrophoresis and bioassay using African green monkey kidney cell were used for identification of TGF-$\beta$ Crude TGF-$\beta$ of 2.75mg was extracted from 5.2g of the platelets by the treatment of acid/ethanol. In gel filtration of crude TGF-$\beta$, 4 peaks were observed at the detection of spectrophotometer at 280nm. Electrophoresis and bioassay identified the 3rd peak TGF-$\beta$. Linear gradient elution from 0 to 3M NaCl in sornipreparative HPLC showed TGF-$\beta$ at 1.5M NaCl. Gel filtration was less expensive and useful method for the purification of TGF-$\beta$.

• 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.