• Archives of Pharmacal Research
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• 제22권1호
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• pp.1-8
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• 1999

Transforming growth factor-$\beta$ (TGF-$\beta$) is the prototypical multifunctional cytokine, participating in the regulation of vital cellular activities such as proliferation and differentiations as well as a number of basic physiological functions. The effects of TGF-$\beta$ are critically dependent on the expression and distribution of a family of TGF-$\beta$ receptors, the TGF-$\beta$ types I, II, and III. It is now known that a wide variety of human pathology can be caused by aberrant expression and function of these receptors. the coding sequence of the type II receptor (RII) appears to render it uniquely susceptible to DNA replication errors in the course of normal cell division. By virtue of its key role in the regulation of cell proliferation, TGF-$\beta$ RII should be considered as a tumor suppressor gene. High levels of mutation in the TGF-$\beta$ RII gene have been observed in a wide range of primarily epithelial malignancies, including colon and gastric cancer. It appears likely that mutation of the TGF-$\beta$ RII gene may be a very critical step in the pathway of carcinogenesis.

• 생물정신의학
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• 제12권2호
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• pp.143-150
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• 2005

목 적: 많은 연구에서 정신분열병에서 염증반응체계의 활성화와 사이토카인의 변화가 병태생리학적 및 원인적 역할을 하는 것으로 보고되어 왔으며, 여기에는 type 1 Thelper cell(Th1), type 2 T helper cell(Th2), type 3 T helper cell(Th3)의 조절 이상이 제시되고 있다. 본 연구에서는 정신분열병 환자에서 항정신병 약물 치료 전후로 Th1 사이토카인인 interleukin-12(IL-12), Th3 사이토카인인 transforming growth factor-${\beta}1$(TGF-${\beta}1$)의 혈장 농도를 측정하였다. 방 법: 23명의 정신분열병 환자군과 31명의 정상대조군에서 IL-12와 TGF-${\beta}1$ 농도를 측정하였고 정신분열병 환자군에서는 8주간 항정신병 약물로 치료 후 다시 IL-12와 TGF-${\beta}1$의 농도를 측정하였다. 또한 정신분열병 환자군에서 치료전과 8주간 치료 후, 2차례에 걸쳐 Brief psychiatric rating scale(BPRS)를 측정하였다. 결 과: 치료전 IL-12 농도와 TGF-${\beta}1$ 농도 모두 정상대조군보다 환자군에서 유의하게 높게 나타났다. 8주간의 치료 후 TGF-${\beta}1$ 농도는 유의하게 감소하여 정상대조군의 농도와 차이를 보이지 않게 된 반면, IL-12의 농도는 유의하지 않은 감소를 보였다. BPRS 점수의 변화 및 IL-12 및 TGF-${\beta}1$의 농도의 변화 사이에는 유의한 상관관계가 없었다. 결 론: 정신분열병의 병태생리학에 사이토카인의 이상이 관여할 수 있으며, TGF-${\beta}1$이 중요한 역할을 하는 것으로 생각된다.

• Clinical and Experimental Reproductive Medicine
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• 제33권2호
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• pp.105-113
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• 2006

목 적: 본 연구를 통해 $TGF-{\beta}1$에 의해 유도된 인간자궁내막의 탈락막화 과정에서 ERK와 $PPAR{\gamma}$의 역할을 규명하고자 하였다. 연구방법: 자궁내막 기질세포는 DMEM/F12 (10% FBS, 1 nM E2 and 100 nM P4) 조건에서 배양하였다. 연구 목적에 따라 $TGF-{\beta}1$ (5 ng/ml), Rosiglitazone (50 nM)와 PD98059 ($20{\mu}M$)를 배양액에 첨가하였다. Trypan-Blue와 hematocytometer를 이용하여 현미경하에서 세포의 개수를 측정하였다. Enzyme-linked immunosorbent assay (ELISA)와 western blotting 방법을 사용하여 단백질의 발현 정도를 관찰하였다. 결과 및 결론: 배양액에 $TGF-{\beta}1$을 첨가하여 세포의 증식 정도를 측정한 결과 $TGF-{\beta}1$이 세포의 증식을 억제하는 것을 알 수 있었다. 또한 배양된 세포로부터 PGE2 및 prolactin의 발현을 유도하는 것을 알 수 있었다. 이러한 $TGF-{\beta}1$의 작용은 Smad 및 ERK의 활성화를 통하여 일어남을 알 수 있었다. $PPAR{\gamma}$의 기질인 rosiglitazone을 배양액에 첨가한 결과 $TGF-{\beta}1$에 의한 세포 증식의 억제가 역전되는 것을 알 수 있었다. 뿐만 아니라, 세포 내 ERK의 활성 역시 억제 시켰으며 이 결과 PGE2와 prolactin의 발현이 억제 되는 것을 관찰할 수 있었다. 따라서 본 연구를 통해 $TGF-{\beta}1$에 의한 자궁내막 기질세포의 탈락막화는 Smad와 ERK의 활성화를 통하여 이루어지며 이러한 과정은 $PPAR{\gamma}$에 의해 억제됨을 알 수 있었다.

• IMMUNE NETWORK
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• 제1권3호
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• pp.260-265
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• 2001

Transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) is a multipotent growth factor affecting development, homeostasis and tissue repair. Many kinds of malignant tissues were reported to overexpress transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) gene. However, a little work has been done on the circulating $TGF-{\beta}1$ and the association of $TGF-{\beta}1$ with progression in patients with malignant tumors. In this study, we measured the plasma level of $TGF-{\beta}1$ in gastric cancer and prostate cancer patients and evaluated the utility of plasma $TGF-{\beta}1$ as a possible tumor marker. We used Enzyme-linked immunosorbent assay (ELISA) system in order to measure plasma $TGF-{\beta}1$ level in 134 gastric cancer patients, 50 prostate cancer patients and 290 normal controls. And the tumor marker, carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), was compared with $TGF-{\beta}1$ in the aspects of sensitivity and specificity. The mean plasma $TGF-{\beta}1$ levels were $1.219{\pm}0.834$ (0.272-5.772) ng/mL in normal controls, $5.964{\pm}3.218$ (0.845-18.124) ng/mL in gastric cancer and $4.140{\pm}2.345$ (1.108-13.302) ng/mL in prostate cancer. In gastric cancer patients difference in plasma $TGF-{\beta}1$ level was not detected according to cancer stage. In comparison with other tumor marker (CEA, PSA) $TGF-{\beta}1$ is more potent in sensitivity. These results indicate that the plasma $TGF-{\beta}1$ level can be a potent tumor marker in gastric cancer and prostate cancer.

• 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.

• Tuberculosis and Respiratory Diseases
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• 제58권3호
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• pp.267-276
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• 2005

연구배경 : 전환성장인자-${\beta}1$(transforming growth factor-${\beta}1$: $TGF-{\beta}1$)은 폐 섬유화를 매개하는 주된 인자이지만 $TGF-{\beta}1$에 의한 폐 섬유화의 발생과 진행기전의 이해는 아직 불완전하다. $TGF-{\beta}1$은 다양한 세포에서 활성산소족(reactive oxygen species: ROS)을 통하여 세포내 신호를 전달하고 ${\alpha}$-smooth muscle actin (${\alpha}$-SMA)의 신생합성을 통하여 상피세포와 폐 섬유아세포를 근 섬유아세포 표현형으로의 변화를 유도하는 주된 인자이다. ROS는 또 다양한 세포에서 세포외기질 (extracellular matrix: ECM) 축적을 유발하는 것이 알려져 있음으로 본 연구에서는 폐 섬유아세포인 MRC-5 세포에서 $TGF-{\beta}1$이 ROS를 매개하여 fibronectin 분비와 ${\alpha}-SMA$ 표현의 증가에 관여하는지를 검색하였다. 방 법 : 성장이 동일화된 MRC-5 세포를 $TGF-{\beta}1$ (0.2-10ng/ml)으로 96 시간까지 자극하였고, 필요에 따라 항산화제인 N-acetylcysteine (NAC)이나 NADPH oxidase 억제제인 diphenyleniodonium (DPI)을 $TGF-{\beta}1$ 투여 1 시간 전부터 전처리하였다. Dichlorofluorescein (DCF)에 민감한 세포내 ROS는 FACS로, 분비된 fibronectin과 세포의 ${\alpha}-SMA$ 표현은 Western blot 분석으로 측정하였다. 결 과 : $TGF-{\beta}1$은 용량의존적으로 fibronectin 분비와 ${\alpha}-SMA$ 표현을 상향조절하였다. NAC와 DPI는 $TGF-{\beta}1$에 의한 fibronectin 분비 증가와 ${\alpha}-SMA$ 상향조절을 유의하게 억제하였다. $TGF-{\beta}1$에 의한 세포내 ROS의 증가도 NAC나 DPI에 의하여 유의하게 억제되었다. 결 론 : 본 연구의 결과는 폐 섬유아세포에서 NADPH oxidase 에 의하여 생산된 ROS가 $TGF-{\beta}1$에 의한 fibronectin 분비와 ${\alpha}-SMA$ 표현을 상향조절함으로써 폐 섬유화의 발생과 진행에 관여할 수 있음을 증명하였다.

• 한국축산식품학회:학술대회논문집
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• 한국축산식품학회 2001년도 임시총회 및 제28차 추계학술발표회
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• pp.43-56
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• 2001

Colostrum contains various kinds of cytokines including TGF-${\beta}$ which is known to be multifunctional in immune response and act as an anti-inflammatory agent. First, we measured the amount of TGF-${\beta}$ in bovine and human colostrum. Expression pattern of TGF-${\beta}$ isotypes was dramatically different between human and bovine colostrial samples. Bovine colostrum collected on day 1 post-delivery retained $41.79{\pm}16.96ng/ml$ of TGF-${\beta}$ 1 and $108.4{\pm}78.65ng/ml$ of TGF-${\beta}$ 2 while in human, $284{\pm}124.75ng/ml$ of TGF-${\beta}$ 1 and $29.75{\pm}6.73ng/ml$ of TGF-${\beta}$ 2. Thus, TGF-${\beta}$ is the predominant TGF-${\beta}$ isotype in bovine colostrum and vice versa in human colostrum. Both TGF-${\beta}$ isotypes diminished significantly in human and bovine colostrum with time. Next, biological activity of colostrial samples was examined in vitro. Both human and bovine colostrum increased IgA synthesis by LPS-activated mouse spleen B cells, which is a typical effect of TGF-${\beta}$ on the mouse B cell differentiation. Futhermore, we found that anti-proliferative activity in MV1LU cells by colostrum samples disappeared by addition of anti-TGF-${\beta}$ 1 and anti-TGF-${\beta}$ 2 antibody. In conclusion, there are substantial amounts of biologically active TGF-${\beta}$ 1 and TGF-${\beta}$ 2 in bovine and human colostrum. The results that the colostrum can increase IgA expression has important implications since IgA is the major Ig class produced in the gastrointestinal tract. We have previously shown that the stimulatory effect of Bifidobacteria bifidum on spllen B cells was quite similar to that of LPS which is a well-known polyclonal activator for murine B cells. In the present study, we further asked whether B. bifidum regulate the synthesis of IgA by mucosal lymphoid cells present in Peyers patches (PP) and mesenteric lymph nodes (MLN). B. bifidum alone, but not C. perfringens, significantly induced overall IgA and IgM synthesis by both MLN and PP cells. This observation indicates that B. bifidum possesses a modulatory effect on the mucosal antibody production in vivo. We, therefore, investigated the mucosal antibody prodduction following peroral administration of B. bifidum to mice. Ingested B. bifidum significantly increased the numbers of Ig (IgM, IgG, and IgA) secreting cells in the culture of both MLN and spleen cells, indicating that peroally introduced B. bifidum enhances mucosal and systemic antibody response. Importantly, however, B. bifidum itself does not induce the own specific antibody responses, implying that B. bifidum do not incite any unwanted immune reaction. Subsequently, it was found that excapsulation of B. bifidum further augments the total IgA production by increasing the number of IgA-secreting cells in the culture of both MLN and spleen cells. Finally, we found that the immuno-stimulating activity of B. bifidum is due to its cell wall components but not due to any actively secreting component(s) from bacteria. Thus our data reveal that peroral administration of B. bifidum can enhance intestinal IgA production and that encapsulation of B. bifidum further reinforces the IgA production.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.79-79
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• 1995

Although synthetic antisense oligodeoxynucleotides (ODNs) have been used to dissect gene function in vitro, technical difficulties of targeted delivery prevented the use of this approach for investigating the effect of gene products in vivo. Here we report the use of local delivery of antisense transforming growth factor-${\beta}$l (TGF-${\beta}$1) oligonucleotides to decrease the fibrosis in the skin wound. Adult wounds heal with scar-tissue formation, whereas fetal wounds heal without scarring and with a lesser inflammatory and cytokine response. We reasoned that strategy emptying antisense TGF-${\beta}$1 ODNs complementary to TGF-${\beta}$1 mRNA might decrease the scarring in dermal wound of mouse. To evaluate this concept, we tested the effects of antisense ODNs targeted to TGF-${\beta}$1 mRNA by topical application of the chemical on the skin wound. Phosphorothioate antisense ODNs was employed to retard their degradation. When antisense TGF-${\beta}$1 ODNs were applied into the wound site, there was a maked reduction of scar compared with control wound site, These effects of antisense TGF-${\beta}$1 ODNs on the scar formation were associated with decreased expression of TGF-${\beta}$1 gene. However sense TGF-${\beta}$l ODNs had no effect on expression of TGF-${\beta}$1 gene. Also, control wounds healed with excessive fibrosis, whereas the antisense treated wounds healed with less fibrosis. In conclusion, our results indicate that antisense TGF-${\beta}$1 ODNs could be used for amelioating scar formation during wound healing.

• 한국잠사학회:학술대회논문집
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• 한국잠사학회 2003년도 International Symposium of Silkworm/Insect Biotechnology and Annual Meeting of Korea Society of Sericultural Science
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• pp.145-146
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• 2003

Overproduction of transforming growth factor (TGF)-$\beta$l has been implicated in the pathogenesis of fibrotic diseases. TGF-$\beta$l plays a crucial role in the accumulation of extracellular matrix (ECM) in human and experimental glomerular diseases. However, it remains unclear whether inhibition of TGF- $\beta$l overproduction would suppress TGF- $\beta$l induced ECM accumulation. To inhibit the overproduction of TGF- $\beta$l in experimental glomerulonephritis induced by anti-Thy 1.1 antibody, we introduced antisense oligodeoxynucleotides (ODN) fur TGF- $\beta$l into the nephritic kidney by the HVJ-liposome-mediated gene transfer method. (omitted)

• Restorative Dentistry and Endodontics
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• 제24권1호
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• pp.200-211
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• 1999

The periapical response to injury is a complex interaction of inflammatory, immune, neural, vascular and synthetic activity. TGF-${\beta}$ is a potent modulator of proliferation and differentiation in various tissue, seems to lead to an increase in extracellular matrix. MMP are a family of proteolytic enzyme that mediate the degradation of extracellular matric macromolecules, but little is known about theirs possible role in periapical tissue. The purpose of this study is to investigate the differential expression of TGF-${\beta}$ and MMP-1 in tooth follicle, periapical abscess, granuloma and cyst. The expression of TGF-${\beta}$ and MMP-1 in Periapical tissue was evaluated by immunohistochemical staining and Western blot analysis. Correlationship among the periapical lesions were stastically analyzed. The degree of MMP-1 expression in periapical abscess was higher than in any other periapical lesion, and stastically significant. TGF-${\beta}$ expression is the prominent in granuloma than other periapical lesion, which was stastically significant. The increased expression of MMP and TGF-${\beta}$ was not co-related with inflammatory cell infiltration degree of the periapical cyst. The expression degree of MMP and TGF-${\beta}$ was not co-related with periapical abscess and cyst, but expression of MMP and TGF-${\beta}$ showed strong positive co-relationship with periapical granuloma, which was stastically significant. TGF-${\beta}$ expression by Western blot analysis was prominent in granuloma and cyst, and similar to the results by imunohistochemistry. MMP-1 expression is less than TGF-${\beta}$, but there is not extreme difference between periapical lesion. These results suggest that TGF-${\beta}$ and MMP may be involved in tissue remodeling and has an important role in progress or mediation of periapical lesions.