• Restorative Dentistry and Endodontics
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• 제32권3호
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• pp.191-197
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• 2007

이 연구의 목적은 치주인대 섬유아세포에 MTA를 접촉시킨 뒤 성장인자 transforming growth factor-beta1 $(TGF-\beta1)$, fibroblast growth factor-2 (FGF-2) 및 cytokine interleukin-6 (IL-6)의 발현량 변화를 측정하는 것이다. MTA군에서는 100 mg씩의 ProRoot MTA와 증류수를 혼합하고, IRM군은 동량의 IRM 분말을 용액에 혼합하여 이 시료들을 경화반응이 진행되도록 7일간 놓아두었다. 사람의 치주인대 섬유아세포를 배양하여 MTA와 IRM시료 상에 well당 $1\times10^5$개 수준으로 도포한뒤 6, 12, 24, 48시간 동안 배양하였다 (n = 5). 대조군으로는 재료의 접촉 없이 배양한 세포를 사용하였다. 시료에서 상층액을 분리하여 $TGF-\beta1$, FGF-2, IL-6의 발현량을 enzyme-linked immunosorbent assay (ELISA)법으로 측정하였다. MTA군에서, 성장인자인 $TGF-\beta1$과 FCF-2는 대조군에 비해 유의성 있게 발현이 억제되었으며 (p < 0.05), cytokine인 IL-6 발현량은 대조군과 유사한 수준으로 나타났다.

• Radiation Oncology Journal
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• 제23권3호
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• pp.161-168
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• 2005

목적: 강력한 항산화 효과를 지닌 melatonin을 전처치하였을 때 방사선유도성 섬유증 과정에서 중요한 사이토카인인 $TGF-{\beta}1$의 변화된 발현양상을 마우스 폐에서 연구하였다. 대상 및 방법: C57BL/6 마우스를 실험군에 따라 세 군(대조군, 방사선조사 단독군, melatonin 전처치군(방사선조사 1시간 전에 300 mg/kg 복강주사))으로 분류하고 양측 흉곽에 12 Gy의 선량을 단일조사하였다. 방사선조사 후 2주와 4주의 폐조직에서 $TGF-{\beta}1$ mRNA 발현수준을 측정하기 위해 semiquantitive RT-PCR를 시행하였고, $TGF-{\beta}1$ protein 발현의 수준과 위치를 보기 위해 면역조직화학염색을 시행하였다. 결과: 2주 후에 측정된 mRNA 발현은 방사선조사 단독군과 melatonin 전처치군에서 각각 대조군의 1.92배와 1.80배 증가된 수준을 보였고(p=0.064), 4주 후에는 각각 2.38배와 1.94배 수준의 증가된 발현을 보였다(p=0.004). $TGF-{\beta}1$ protein의 발현은 조직병리학적으로 방사선손상 영역에서 주로 관찰되었는데 폐포 대식세포와 폐포벽의 상피세포들이 주요 근원이었다. 발현수준은 2주완 4주 후에 각각 $15.8\%\;vs\;16.9\%$ (P=0.565), 그리고 $36.1\%\;vs\;25.7\%$ (p=0.009)이었다. 결론: Melatonin 전처치로 방사선조사에 의한 $TGF-{\beta}1$ mRNA와 protein의 발현이 4주 후에 유의하게 감소됨을 관찰하였다. 따라서 방사선으로 인한 폐손상 시에 항섬유증 약물로의 사용가능성을 확인하였다.

• 한국수정란이식학회지
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• 제11권2호
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• pp.111-124
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• 1996

The present study was carried out to investigate the effects of co-culture cells and growth factors on in vitro culture of Korean native cattle(KNC) embryos fertilized in vitro. Two-eight cell embryos were cultured in vitro using 4 types of co-culture cells and 3 growth factors singly or in combination. The results were as follows, In the co-culture of 2~8 cell embryos with bovine oviductal epithelial cell(BOEC), granulosa cell(BGC), uterine epithelial cell(BUEC) and mouse embryonic fibroblast (MEF) monolayers, the developing rate to blastocysts was significantly(P<0.05) higher with BUEC(32.1%) than with MEF(15.3%), BGC(13.2%) and non co-culture control(11.6%). When the morula co-cultured with BOEC for 5 days following in vitro fertilization were co-cultured with BOEC continuously or with BUEC, respectively, the developing rate to blastocysts was higher with BUEC(73.9%) than with BOEC(56.0%). To examine the effects of growth factors on in vitro development of 2~8 cell embryos, epidermal growth factor(EGF), transforming growth factor-$\beta$l(TGF-$\beta$l) and insulin-like growth factor-1(IGF-1) were added singly or in combination to TCM 199 maturation medium with respective concentration. In a addition of each 10, 30 and SOng /rnl EGF, the developing rate to blastocysts was the highest in lOng /ml EGF(25.3%). In addition of each 1, 2 and Sng /mi TGF-$\beta$1, the developing rate to blastocysts was the highest in lng /ml TGF-$\beta$1(28.8%). In addition of each 50, 100ng/ml JGF-l, the developing rate to blastocysts was higher in 100ng/ml IGF-l(16.5%) than in SOng/mi IGF-1(12.9%). When lOng /ml EGF and lng /ml TGF-$\beta$l was added singly or in combination, the developing rate to blastocysts was similar in groups added singly or in combination with EGF and TGF-$\beta$l (23.l~24.6%), although higher than in control(16.7%). In the co-culture of 2~8 cell embryos Wth BOEC + each 10, 30 and 5Ong /rnl EGF, the developing rate to blastocysts was significantly(p<0.05) higher in BOEC + long /ml EGF(32.3%) than in BOEC + 3Ong /ml EGF(18.9%) and BOEC + song /ml EGF(9.7%). In the co-culture of 2~8 cell embryos with BOEC + each 1, 2, Sng /ml TGF-$\beta$l the developing rate to blastocysts was higher in BOEC + Sng/rnl TGF-$\beta$l(28.2%) than in BOEC + lng /ml TGF-$\beta$l(21.7%) and BOEC + 2ng/ml TGF-$\beta$l(21.4%). In summary, higher developing rate to blastocysts were obtained with co-culture of BUEC for co-culture system, with addition of lOng /ml EGF or lng /ml TGF-$\beta$l for growth factor culture system, and with co-culture of BOEC + lOng /ml EGF or BOEC + Sng /ml TGF-$\beta$l for co-culture + growth factor culture system.

• Preventive Nutrition and Food Science
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• 제6권2호
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• pp.126-132
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• 2001

Methanol extracts form four kinds of kimchi, which were differently prepared in kinds and levels of sub-ingredients, were given to Balb/c mice for 3 weeks (0.5 mg/kg/day). Peritoneal macrophages isolated from mice treated with kimchi extracts and saline were stimulated by lipopolysaccharide (LPS). K3 and K4 kimchis, containing more red pepper powder, garlic, Chinese pepper powder, mustard leaf and organically cultivated Korean cabbage, significantly increased NO production by the activated macrophages (p<0.05). K1, K2, K3 and K4 kimchi extracts (0.01, 0.1, 1.0 $\mu\textrm{g}$) significantly reduced the increased TGF-$\beta$1 production of H.pylori lysate (0.01 $\mu\textrm{g}$)-activated human epithelial RPMI 2650 cells (5$\times$10$^{4}$ cells/mL) at 24 and 48 hrs of treatment (p<0.01). However, the decreased TGF-$\beta$1 $\alpha$ production of RPMI 2650 cells by H. pylori lysate increased by treatment with kimchi extract for 72 hrs. Especially, K4 kimchi (containing organically cultivated Korean cabbage and more ingredients, modulated TGF-$\beta$1 production of H. pylori lysate-activated RPMI 2650 cells to the normal level (control) by treatment for 48 hrs. The treatment of K1 and K4 kimchi enhanced the LPS (0.01 $\mu\textrm{g}$/mL)-induced IL-6 production of splenocytes. The results suggest that kimchi might have an beneficial effect on cancer prevention due in part to the function enhancing NO production of activated macrophages. Our data suggest that kimchi could modulate TGF-$\beta$1 production by cancer cells and IL-6 production of splenocytes, thereby possibly contributing to control carcinogenesis and the immune system.

• BMB Reports
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• 제45권9호
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• pp.509-514
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• 2012

We have found that the previously uncharacterized bone morphogenetic protein-9 (BMP9) is one of the most osteogenic factors. However, it is unclear if BMP9 cross-talks with $TGF{\beta}1$ during osteogenic differentiation. Using the recombinant BMP9 adenovirus, we find that low concentration of rh$TGF{\beta}1$ synergistically induces alkaline phosphatase activity in BMP9-transduced C3H10T1/2 cells and produces more pronounced matrix mineralization. However, higher concentrations of $TGF{\beta}1$ inhibit BMP9-induced osteogenic activity. Real-time PCR and Western blotting indicate that BMP9 in combination with low dose of $TGF{\beta}1$ potentiates the expression of later osteogenic markers osteopontin, osteocalcin and collagen type 1 (COL1a2), while higher concentrations of $TGF{\beta}1$ decrease the expression of osteopontin and osteocalcin but not COL1a2. Cell cycle analysis reveals that $TGF{\beta}1$ inhibits C3H10T1/2 proliferation in BMP9-induced osteogenesis and restricts the cells in $G_0/G_1$ phase. Our findings strongly suggest that $TGF{\beta}1$ may exert a biphasic effect on BMP9-induced osteogenic differentiation of mesenchymal stem cells.

• Clinical and Experimental Reproductive Medicine
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• 제34권3호
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• pp.139-148
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• 2007

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.273-276
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• 2014

Ellagic acid has been shown to inhibit tumor cell growth. However, the underlying molecular mechanisms remain elusive. In this study, our aim was to investigate whether ellagic acid inhibits the proliferation of MCF-7 human breast cancer cells via regulation of the TGF-${\beta}$/Smad3 signaling pathway. MCF-7 breast cancer cells were transfected with pEGFP-C3 or pEGFP-C3/Smad3 plasmids, and treated with ellagic acid alone or in combination with SIS3, a specific inhibitor of Smad3 phosphorylation. Cell proliferation was assessed by MTT assay and the cell cycle was detected by flow cytometry. Moreover, gene expression was detected by RT-PCR, real-time PCR and Western blot analysis. The MTT assay showed that SIS3 attenuated the inhibitory activity of ellagic acid on the proliferation of MCF-7 cells. Flow cytometry revealed that ellagic acid induced G0/G1 cell cycle arrest which was mitigated by SIS3. Moreover, SIS3 reversed the effects of ellagic acid on the expression of downstream targets of the TGF-${\beta}$/Smad3 pathway. In conclusion, ellagic acid leads to decreased phosphorylation of RB proteins mainly through modulation of the TGF-${\beta}$/Smad3 pathway, and thereby inhibits the proliferation of MCF-7 breast cancer cells.

• Tuberculosis and Respiratory Diseases
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• 제44권4호
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• pp.871-888
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• 1997

연구배경 : 특발성 폐 섬유화확 병인론으로 폐포염과 폐에 침윤한 염증세포 및 폐 조직자체의 실질세포들이 성장인자를 포함한 다양한 cytokine을 분비하여 실질조직을 구성하는 세포에 손상을 야기함으로써 종국에는 섬유화를 초래하는 것으로 이해하고 있다. 그러나 이들에 대한 개괄적인 연구가 부족하고 매개체 각각에 대한 단편적인 논문들뿐이어서 본 연구에서는 BLM유도 폐 손상및 섬유화의 발생기전에 있어서 IL-1, IL-6, TNF-$\alpha$와 TGF-${\beta}_1$, PDGF, bFGF들의 역할을 규명하고자 하였다. 방 법 : Wistar백서를 정상대조군, BLM투여군, BLM과 비타민 E병합투여군으로 나누었고 BLM 투여후 제 1, 2, 3, 4, 5, 7, 14, 21, 28일에 각각 도살한 다음 기관지폐포 세척술을 시행하여 시기별 총 세포수, 세포 구성성분비율을 살펴보았고 TGF-${\beta}_1$, PDGF, bFGF, IL-1, IL-6, TNF-$\alpha$에 대한 면역조직화학 염색, TGF-${\beta}_1$ mRNA에 대한 동소보합결합검사를 시행, 각 매개체의 생성소, 발현분포 및 정도를 분석하였다. 결 과 : BLM 투여후 1~7 일에 중성구와 기관지상피세포에서 생성된 IL-1, IL-6는 폐손상부위로 원하는 것으로 생각되며 7일이내에 기관지상피세포에서의 IL-1, IL-6 의 양성발현은 기관지상피세포가 BLM 유도 폐 섬유화시 기도주변에서 일어나는 염증 및 면역반응을 항진 및 유지시키는 간접증거로 생각된다. TNF-$\alpha$는 BLM투여후 1~5일에는 기관지상피세포, 중성구가 주생성소로 폐손상부위로의 염증세포의 이동에 주요역할을 하는 것으로 생각되며 7~28일에는 대식세포가 주생성소로서 섬유화를 촉진시키는 것으로 생각된다. TGF-${\beta}_1$은 기관지 상피세포, 대식세포가 주생성소로서 섬유모세포가 표적세포로 생각되며 섬유모세포가 세포외 기질을 생성하도록 자극하고 대식세포에서 유리된 PDGF와 함께 섬유모세포의 증식을 자극한다. 대식세포 및 섬유모세포에서 유리된 bFGF는 TGF-${\beta}_1$과 함께 교원질과 같은 세포외기질의 생성을 자극하는 것으로 여겨진다. 비타민 E와 BLM 병합투여군의 경우 6가지 성장인자 및 cytokine의 발현세포는 같았으나 발현세포수는 극히 미미하였고 trichrome염색상 섬유화도 미약하였다. 결 론 : BLM으로 인한 혈관내피 및 폐포상피세포 손상이후 침윤한 중성구 및 기관지 상피세포가 IL-1, IL-6, TNF-$\alpha$를 분비하여 BLM투여 1~7 일에 많은 수의 중성구를 동원하도록 유도하며 이들이 유리하는 다양한 효소 및 산소유리기가 폐의 정상구조를 파괴하여 섬유화를 시작하게 하는 것으로 생각한다. 손상이 진행됨에 따라 BLM투여 7~28 일에 대식세포가 유리하는 TGF-${\beta}_1$, PDGF, bFGF, TNF-$\alpha$는 섬유모세포를 자극, 이들의 증식을 유도하고 또한 세포외기질의 생성증가를 유도하여 폐 섬유화를 진행시키는 것으로 사료되며 TNF-$\alpha$는 BLM투여후 전 기간에 걸쳐 다수의 세포에서 발현된 점으로 미루어 섬유화에 있어서 TGF-${\beta}_1$ 못지않은 중요한 역할을 하는 것으로 여겨진다. 또한 비타민 E가 BLM유도 폐 손상으로 인한 폐 섬유화의 정도를 감소시키는 것으로 생각한다.

• 대한치과의사협회지
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• 제46권8호
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• pp.494-504
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• 2008

Osseointegration is a result of bone formation and bone regeneration process, which take place at the interface between bone and implant and biologic determinants such as cytokine, growth factors, bone matrix proteins play an important role in osseointegration. The purpose of this study is to compare the expressoin of TGF-$\beta$, IGF-I, BMP2, BMP4 during osseointegration. We designed an experimental group which was inserted with a RBM surface titanium implants and machined surface, and compared with a control group which had a simple bone cavity and normal bone. Titanium implants were placed into tibia of 8 rabbits. We compared the expression of TGF-$\beta$, IGF-I, BMP2, BMP4 using RT_PCR (reverse transcriptase chain reaction)analysis in day 3,7,14 and 28 of implant insertion. According to the results, growth factors of experimental groups were more expressed than control groups. Among experimental groups, expression of TGF-$\beta$, IGF-I, BMP4 of BMP group had tedency to increase more at 14th, 28th days than Machined surface group. Therefore, our results suggest that TGF-$\beta$, IGF-I, BMP4 are expressed within the bone around the implant and more increased around rough surface implants while osseointegration occurs after dental implant insertion.

• Tuberculosis and Respiratory Diseases
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• 제79권3호
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.