• The Journal of Korean Physical Therapy
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• 제22권3호
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• pp.87-92
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• 2010

Purpose: The purpose of this study was to investigate the effect of electrical stimulation (ES) on the wound closure rate, collagen deposition, and TGF-${\beta}$1 mRNA expression in skin wound of rat. Methods: Twenty male Sprague-Dawley rats (222~271 g) were randomly divided into ES (n=10) and control group (n=10). The ES group received a cathodal stimulation with 50 V at 100 pps for 30 minutes for 7 days, while the control group was not given electrical stimulation. The wound closure rate, collagen density and TGF-${\beta}$1 mRNA ratio were measured. Results: The mean wound closure rates in the ES and control groups were $83.79{\pm}16.35$% and $51.57{\pm}17.76$%, respectively (p<0.001). The collagen density in the ES and control groups were $46.67{\pm}10.68$% and $25.03{\pm}13.09$%, respectively (p<0.001). The TGF-${\beta}$1 mRNA ratio in the ES and control groups were $1.35{\pm}0.60$ and $0.63{\pm}0.30$, respectively at 6 hours post-wound (p<0.01) and $1.69{\pm}0.47$ and $1.32{\pm}0.28$, respectively, at 7 days post-wound (p<0.05). Conclusions: ES accelerated the wound closure rate of skin incision wounds and was accompanied by an increase in collagen deposition in the regenerating dermis. In addition, ES increased TGF-${\beta}$1 mRNA expression during wound healing process. These findings suggest that ES may activate TGF-${\beta}$1 expression, and may increase synthesis activities of fibroblasts in regenerating skin wounds in rats.

• BMB Reports
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• 제29권5호
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• pp.405-410
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• 1996

Previous studies have shown that transforming growth factor beta ($TGF-{\beta}$) is a potent regulator of cell growth and differentiation. To study the effects of $TGF-{\beta}$ on cell morphology and cytoskeleton reorganization, we conducted a survey using Mv1Lu mink lung epithelial cells with antibodies to cytoskeletal proteins and an extracellular matrix protein. While the untreated cells showed a cuboidal shape of typical epithelia, the Mv1Lu cells displayed a drastic shape change in the presence of $TGF-{\beta}$. This alteration was most prominent when near-confluent cells were treated with $TGF-{\beta}$. Since the morphology alteration is known to be accompanied by the reorganization of cytoskeletal proteins in other cell types, we investigated the intracellular distribution of the three major cytoskeletal structures: microfilaments, microtubules, and intermediate filaments. In the microfilament system, $TGF-{\beta}$ induced new stress fiber formation, which was caused primarily by the polymerization of cytoplasmic G-actin. However, $TGF-{\beta}$ appeared not to induce any significant changes in microtubular structures and vimentin filaments as determined by indirect fluorescence microscopy. Finally we confirmed the rapid accumulation of fibronectin by immunoblot analysis and chased the protein locations by immunofluorescence microscopy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권3호
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• pp.199-203
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• 2007

Several matrix metalloproteinases (MMPs) have been shown to play an important role in the invasion and metastasis of oral squamous cell carcinoma (OSCC). The members of the TGF-$\beta$ signaling pathway are being considered as predictive biomarkers for progressive tumorigenesis and molecular targets for the prevention and the treatment of cancer and metastasis. The aim of the present study was to find the clinical significance of the expression of TGF-${\beta}1$ and MMP-2 related to the regional lymph node metastasis in OSCC. This study included 76 cases of primary OSCC, of which 42 cases showed regional lymph node metastases. Immunohistochemistry was used for the localization of protein. The relation between the expression of each protein and clinical variables was statistically evaluated. In results, the expression of TGF-${\beta}1$ both main mass with lymph node metastasis and without lymph node metastasis was found not to be statistically significant (p>0.05). The expression of MMP-2 was found to be statistically significant related to regional lymph node metastasis (p<0.05). When compared the expression in the metastatic lymph node, TGF-${\beta}1$ was significantly highly expressed than MMP-2 (p<0.05). In conclusion, the expression of MMP-2 was significantly elevated in patients with lymph node metastasis as compared to the patients without lymph node metastasis, which could be useful in predicting the risk of lymph node metastasis in OSCC.

• The Journal of Korean Physical Therapy
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• 제14권4호
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• pp.87-94
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• 2002

Low intensity laser irradiation is potential physical agent that triggers the muscle regeneration by previous study. In muscle regeneration, a number of growth factors also promotes that is triggered in response to muscle damage. The transforming growth factor(TGF)-$\beta$ is involved in the activation of cell proliferation and the inhibition of cell differentiation in muscle regeneration. This is secreted not only autocrine system but also paracrine and endocrine. Therefore, We investigated that effects of Gallium aluminum arsenide(GaAlAs) diode laser for the expression of TGF-$\beta$ on lumbar spinal cord after extensor digitorum muscle crush injury. After laser irradiation, the immunoreactivity of TGF-$\beta$ was increased bilaterally in gray mater of spinal cord. Especially, in 1 day, experimental group was highed than control, and in 3 day, lateral motor nucleus were storong immunoreactivy of TGF-$\beta$. Also, in 1 and 2 day, TGF-$\beta$ was showed in white mater as well as gray mater, but in 3 day, only showed in gray mater. These data may suggests to the establishment of laser irradiation on spinal cord for skeletal muscle injury.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권2호
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• pp.123-130
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• 2005

Many of the molecular and genotypic events taking place at the osteoblast cell level during bone-implant integration are still largely unknown. The objective of this study was to examine expression patterns of TGF-$\beta$ and IGF-I related genes during bone-implant integration. Titanium implants with machined surface were placed into 8 rabbit tibias. At 3rd, 7th, 14th, 28th day after implantation, the expression pattern of TGF-$\beta$ and IGF-I genes in bone with or without implant was examined using reverse transcriptase-polymerase chain reaction (RT-PCR). At the same time, histomorphometric analysis was evaluated, respectively. The bone-to-implant contacts (BIC) of experimental groups were 5.2%, 6.2%, 6.6%, 24.6% at 3rd, 7th, 14th, 28th day. This indicated that newly formed bone increased at the implant surface in bone marrow space after implantation. The expressions of TGF-$\beta$ and IGF-I were higher in implantation groups than untreated control groups during all experimental days. The increased expression of TGF-$\beta$ and IGF-I genes may be associated with the increased bone-to-implant contact. This result provided the evidence for existing biologic differences in tissue response after implantation and helped us to understand molecular biologic processes in tissue-implant integration.

• Biomolecules & Therapeutics
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• 제32권4호
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• pp.432-441
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• 2024

Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.

• Radiation Oncology Journal
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• 제19권2호
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• pp.190-198
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• 2001

목적 : Captopril을 방사선조사와 병용하여 조기 폐손상을 감소시킬 수 있는 방사선보호제로서의 역할을 확인하고 $TNF\alpha$와 $TGF\beta1$이 방사선 보호기전에 관여하는지를 알아보고자 하였다. 대상 및 방법 : 실험동물(Sprague-Dawley 흰쥐)은 정상대조군, 실험군(방사선 단독군, Captopril과 방사선 병용군)으로 분류하였다. 실험군은 12.5 Gy의 방사선을 좌측 흉곽에 단일조사 하였다. Captopril과 방사선 병용군은 Captopril (50 mg/kg/d)을 방사선조사 1주전부터 실험종료시인 8주까지 식수에 섞어 경구 투여하였다. 실험결과는 방사선조사 2주와 8주 후에 병리조직 소견을 분석하였고 면역조직화학염색으로 $TNF\alpha$와 $TGF\beta1$의 발현을 관찰하였다. 결과 : 방사선조사 2주 후에, Captopril과 방사선 병용군은 방사선 단독군에 비해 폐포강내 출혈, 폐포 상피세포 변화, 기관지 상피세포 변화, 혈관변화, 혈관주위 부종과 같은 조직소견의 정도가 현저히 감소되었다. 방사선조사 8주 후에는 기관지 상피세포 변화와 혈관주위 부종이 방사선 단독군에 비해 적었다. Captopril과 방사선 병용군에서 방사선조사 2주후 $TNF\alpha$의 발현은 방사선 단독군과 비교시 폐포 상피세포(p<0.01) 및 폐포강의 대식세포(p<0.01)에서 현저히 감소되었고, 기관지 주변의 림프조직(p=0.06)에서는 감소하는 경향이었다. $TGF\beta1$은 폐포상피세포(p<0.02) 및 폐포강의 대식세포(p<0.02)에서 양성세포가 현저히 감소되었다. 방사선 단독군과 비해 8주후 Captopril과 방사선 병용군의 $TNF\alpha$는 차이가 없었고, $TGF\beta1$의 발현은 폐포강의 대식세포(p=0.09)에서만 감소하는 경향이었다. 결론 : 흰쥐의 폐에 Captopril을 방사선과 병용투여하여 병리조직 소견을 관찰한 결과 방사선에 의한 조기 폐손상이 감소됨을 확인할 수 있었다. 또한 방사선조사 2주 후는 $TNF\alpha$와 $TGF\beta1$의 발현이 감소하고, 8주 후에는 $TGF\beta1$ 발현의 감소가 관찰되어, Captopril이 조기 폐손상을 억제하는 방사선보호제로서 기전의 일부에 $TNF\alpha$와 $TGF\beta1$이 관여함을 확인할 수 있었다.

• Clinical and Experimental Reproductive Medicine
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• 제35권1호
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• pp.49-60
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• 2008

목 적: 자궁내막조직에서 분리한 상피세포와 기질세포를 삼차원 공배양을 통한 탈락막화 유도에서 성호르몬과 TGF-${\beta}1$의 역할을 알아보고 2-세포기 생쥐배아와 탈락막화가 유도된 자궁내막세포와의 공배양을 통하여 포배형성율, 부화율, 포배기배아의 내세포괴와 영양막세포수 및 부착율을 알아보기 위해 시행되었다. 연구방법: 인간 자궁내막조직에서 분리된 기질세포와 상피세포의 표지인자인 cytokeratin과 vimentin에 대한 면역조직 화학염색을 실시하여 분리를 확인하였으며, 성호르몬 우세환경 (progesterone, estrogen)에서 분리된 세포를 단일배양 혹은 3차원 공배양을 통하여 RT-PCR법으로 TGF-${\beta}1$, 수용체-1, -2, integrin-${\beta}3$, prolactin의 발현을 조사하였다. 배양액군을 대조군으로 하여 2-세포기 생쥐배아와 탈락막화 유도와 유도하지 않은 인간 자궁내막세포와의 공배양을 통하여 포배형성율, 부화율, 부착율과 부화된 포배의 영양막세포와 내세포괴수를 비교하였다. 결 과: 상피세포 표지인자인 cytokeratin과 기질세포 표지인자인 vimentin을 이용하여 면역조직화학염색을 한 결과 각각 95% 이상에서 양성반응을 나타내어 자궁내막조직으로부터 상피세포와 기질세포가 성공적으로 분리되었음을 확인하였다. 분리된 상피세포와 기질세포를 단일배양에서는 성호르몬의 조건에 관계없이 TGF-${\beta}1$과 수용체 type-1, type-2, integrin-${\beta}3$, prolactin mRNA가 발현되지 않았다. 공배양에서는 progesterone 우세환경일 경우 TGF-${\beta}1$ 수용체 type-2를 제외한 모든 mRNA가 발현하였으나 estrogen 우세환경에서는 TGF-${\beta}1$ 수용체 type-2와 prolactin이 발현되지 않았다. 2-세포기 생쥐배아를 배양액군, 비탈락막군 및 탈락막군으로 나누어 공배양하였을 때 포배기 발달율은 차이가 없었으나 부화율 (92%)과 부착율 (82%)은 탈락막군이 유의하게 높았으며 (p<0.05), 비탈락막군의 공배양에서 다수의 영양막세포가 투명대를 완전히 빠져나오지 않은 상태로 부착한 비정상형태를 보였다. 부화된 생쥐 포배기배아의 내세포괴수는 탈락막화에 관계없이 공배양한 포배의 내세포괴수가 유의하게 많았으며 (p<0.05), 영양막세포수는 탈락막군에서 배양액군과 비탈락막군보다 유의하게 많았다 (p<0.05). 결 론: 자궁내막조직에서 상피세포와 기질세포를 분리하여 다시 삼차원적 공배양을 통하여 progesterone (100 nM), estrogen (1 nM)과 TGF-${\beta}1$ (10 ng/ml)을 첨가하면 체외에서 탈락막화를 유도할 수 있으며, 탈락막화를 유도한 자궁내막 세포와 2-세포기 생쥐배아를 공배양하였을 때 탈락막화가 부화율, 부착율 및 영양막세포수에 유효한 영향을 미치는 것을 알 수 있었다.

• 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.

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