• 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-$\beta$.

• 한국동물학회지
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• 제38권1호
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• pp.20-25
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• 1995

계배 limb bud 간충직 연골원성 세포로부터 연골세포로의 분화에 미치는 transforming growth factor-f2(TGF-$\beta$2)의 영향을 알아보기 위하여, Hamburger-Hamilton stages 23/24의 간충직 세포들을 미세배양법으로 배양하면서. TGF-$\beta$2의 농도 및 처리시간에 따른 연골세포의 분화에 미치는 영향을 조사하였다 그 결과 TGF-$\beta$2는 배양 첫 24시간 동안 1-2 ng/ml의 농도로 처리하였을 때 가장 효과적으로 연골세포의 분화를 촉진하였으며, 또한 TGF-$\beta$2의 처리군에서 배양 3일째에 tsss) sulfate의 glycosaminoglvcan으로의 유입량이 현저히 증가함을 보였다 한편. 배양 48시간내에TGF-$\beta$2를 처리한 경우 분화를 촉진 유도한 반면, 배양 48시간 이후에 처리하였을 때에는 분화 촉진 효과가 나타나지 않았다. 이상의 결과로부터 TGF-$\beta$2는 연골원 세포의 분화 초기단계에 세포외기질의 합성을 촉진시켜 세포응축을 유발하고. 세포-세포 및 세포-세포외기질의 상호작용을 증대시킴으로써 연골세포로의 분화를 촉진시킬 것으로 추정되었다.

• Journal of Periodontal and Implant Science
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• 제25권3호
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• pp.720-732
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• 1995

미분화중배엽세포의 분화에 관여한다고 알려진 변형성장인자-${\beta}1$이 초기배양한 치주인대세포와 치은섬유아세포에 각기 다른 농도와 시간에 따라 변형성장인자-${\beta}1$을 주입했을때 두 세포의 세포증식능에 미치는 영향을 알아보고 각 조건에 따른 두 세포간의 증식능을 상호 비교해 보고자 본 실험을 실시하였다. 교정치료를 목적으로 내원한 환자의 제 1 소구치 부위의 정상치은을 절제하고, 건강한 제 1 소구치를 발거하여 치은섬유아세포와 치주인대세포를 분리, 배양하여 변형성장인자-${\beta}1$을 주입시키지 않은 군을 대조군으로 하고, 변형성장인자-${\beta}1$을 각각 0.25, 0.5, 1, 2.5, 5ng/ml로 주입시킨 군을 실험군으로하여 24시간, 48시간, 72시간 동안 배양하였으며, 각 시간별 배양 24시간 전에 $1{\mu}Ci/ml$ $[^3H]-thymidine$을 첨가하여 $[^3H]-thymidine$이 DNA내로 편재되는 속도로써 두세포군의 증식능을 측정하여 다음과 같은 결과를 얻었다. DNA합성능에 미치는 변형성장인자-${\beta}1$의 효과는 치주인대세포와 치은섬유아세포 모두에서 투여한 변형성장인자-${\beta}1$의 효과는 치주인대세포와 치은섬유아세포 모두에서 투여한 변형성장인자에 대하여 농도의존적으로 세포가 증식 하는 것으로 나타났다. 치은섬유아세포에 변형성장인자-${\beta}1$을 투여한 군에서는 24, 48, 72시간 모두에서 각 대조군에 비하여 농도의존적으로 증가하는 경향을 보였다. 24시간 적용시 대조군에 비해 1,2.5, 5 ng/ml투여군에서 통계적으로 유의한 차이(P<0.05)를 나타내었고, 48시간 적용시에는 대조군에 비해 1, 2.5, 5 ng/ml 투여군에서 통계적으로 유의한 차이(P<0.05)를 나타내었다. 48시간 적용시에 가장 높은 증식능을 보였으며 72시간 적용시에는 48시간 적용에 비해 전반적으로 증식능이 감소하는 경향을 보였다. 치주인대세포의 DNA 합성능에 미치는 변형성장인자-${\beta}$의 효과는, 변형성장인자-${\beta}$를 각각 24시간, 48시간 적용하였을�� 각 대조군에 비하여 농도의존적으로 증가하는 경향을 보였으며, 24시간 적용시에 대조군에 비해 1, 2.5, 5ng/ml 투여군에서 통계적으로 유의한 차이(P<0.05)를 나타내었고, 48시간 적용시에 대조군에 비해 2.5, 5ng/ml 투여군에서 통계적으로 유의한 차이(P<0.05)를 나타애었다. 72시간 적용시에는 5ng/ml의 농도에서 증식능이 감소하는 경향을 보였다. 48시간 적용시에 역시 가장 높은 증식능을 보였으며 72시간 적용에서는 48시간 적용에 비해 전반적으로 증식능이 감소되는 경향을 나타내었다. 변형성장인자-${\beta}1$의 적용에 따른 치주인대세포와 농도별 비교에서 치은섬유아세포군이 치주인대세포군보다 더 높은것으로 나타났다.

• Archives of Plastic Surgery
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• 제40권6호
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• pp.676-686
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• 2013

Background To overcome the potential drawbacks of a short half-life and dose-related adverse effects of using active transforming growth factor-beta 1 for cartilage engineering, a cell-mediated latent growth factor activation strategy was developed incorporating latent transforming growth factor-${\beta}$1 (LTGF) into an electrospun poly(L-lactide) scaffold. Methods The electrospun scaffold was surface modified with NH3 plasma and biofunctionalised with LTGF to produce both random and orientated biofunctionalised electrospun scaffolds. Scaffold surface chemical analysis and growth factor bioavailability assays were performed. In vitro biocompatibility and human nasal chondrocyte gene expression with these biofunctionalised electrospun scaffold templates were assessed. In vivo chondrogenic activity and chondrocyte gene expression were evaluated in athymic rats. Results Chemical analysis demonstrated that LTGF anchored to the scaffolds was available for enzymatic, chemical and cell activation. The biofunctionalised scaffolds were non-toxic. Gene expression suggested chondrocyte re-differentiation after 14 days in culture. By 6 weeks, the implanted biofunctionalised scaffolds had induced highly passaged chondrocytes to re-express Col2A1 and produce type II collagen. Conclusions We have demonstrated a proof of concept for cell-mediated activation of anchored growth factors using a novel biofunctionalised scaffold in cartilage engineering. This presents a platform for development of protein delivery systems and for tissue engineering.

• Journal of Periodontal and Implant Science
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• 제26권2호
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• pp.429-447
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• 1996

Transforming growth factor $-{\beta}$ is one of the polypeptide growth factors that mediate the activity of mesenchymal cells and regulate wound healing process via cell proliferation, migration and extracellular matrix formation. The purposes of this study is to evaluate the effects of transforming growth factor $-{\beta}$ on the protein synthetic activity of human periodontal ligament cells and human gingival fibroblasts. The cells which were prepared were primary cultured gingival fibroblasts and periodontal ligament cells from humans, and the fourth or sixth subpassage were used in the experiments. Cells were seeded and at a confluent state, 0, 0.5, I, 2.5, 5, 10 ng/ml $TGF-{\beta}$ and $2{\mu]Ci/ml\;[^3H]$ proline were added to the cells and cultured for 24 hours. Then, 1 and 5 ng/ml concentrations were selected and added to confluent cells and cultured for 24 and 48 hours. They were labeled with $2{\mu}Ci/ml\;[^3H]$ proline for 24 hours and a collagen assay was done by the Peterkofsky and Diegelman method. The results were presented as the mean disintegration per minute (dpm) per well and S.D. of four determinations, The results were as follows. : The total protein, collagen and noncollagenous protein synthesis in periodontal ligament cells and gingival fibroblasts were increased dose- dependently by transforming growth factor-p to 2.5-5 ng/ml concentration and decreased at 10 ng/ml concentration. The percent of collagen was slightly changed according to the concentration of transforming growth factor-po The effect of transforming growth $factor-{\beta}$ was not specific for collagen synthesis since it increased the total, noncollagenous and collagenous protein, simultaneously. In the comparison of protein synthetic activity between the human periodontal ligament cells and human gingival fibroblasts, the human gingival fibroblasts had higher activities than the human periodontal ligament cells at all times and concentrations of $TGF-{\beta}$. In the comparison of protein synthetic activity between the 24 hour effect and the 48 hour effect of $TGF-{\beta}$, the 48 hour cultured cells' synthetic activity decreased more than the 24 hour cultured cells at human periodontal ligament cells and human gingival fibroblasts. In conclusion, $TGF-{\beta}$ has important roles in the stimulation of protein synthesis in human periodontal ligament cells and human gingival fibroblasts. Thus, it may be useful for clinical application in periodontal regenerative procedures.

• Toxicological Research
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• 제16권1호
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• pp.59-61
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• 2000

A single nucleotide polymorphism in the transforming growth factor-$\beta$ type II receptor (TGE$\beta$RII) gene of the rat was studied. TGF$\beta$RII is a tumor suppressor that is frequently inactivated by mutation in human colon cancers. A novel nucleotide polymorphism of G to A(or A to G), which causes a silent mutation at codon 129, was found in G:C rich sequence in the TGF$\beta$RII gene of Sprague-Dawley rats. The results suggest that genetic polymorphism occures without a strain of the laboratory animal.

• Journal of Oral Medicine and Pain
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• 제25권1호
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• pp.53-62
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• 2000

Bone marrow culture systems are widely used to differentiate osteoclast-like cells in vitro using several osteotropic hormones. In this study, we isolated and cultured the mouse bone marrow cells with or without some osteotropic hormones such as parathyroid hormone(PTH), prostaglandin $E_2(PGE_2)$ and $l,25(OH)_2-vitamin$ $D_3$(Vit. $D_3$). We confirmed the formation of osteoclast-like cells morphologically and functionally by the expression of tartrate-resistant acid phosphatase(TRAP) and by their capability to resorb dentin slices. We also studied the effects of transforming growth $factor-{\beta}(TGF-{\beta})$ and epidermal growth factor(EGF) on the Vit. $D_3-induced$ osteoclast-like cell formation. In control, a few multinucleated cells were formed whereas PTH and $PGE_2$ increased the number of multinucleated cells. PTH, $PGE_2$ and Vit. $D_3$ induced the formation of TRAP-positive multinucleated cells. After culture of mouse bone marrow cells on the dentin slices with or without osteotropic hormones, giant cells with diverse morphology were found on the dentin slices under the scanning electronmicroscopy. After removing the attached cells, resorption pits were identified on the dentin slices, and the shape of resorption pits was variable. EGF increased the osteoclast-like cell formation induced by Vit. $D_3$, however, $TGF-{\beta}$ showed biphasic effect, which at low concentration, increased and at high concentration, decreased the osteoclast-like cell formation induced by Vit. $D_3$.

• Archives of Plastic Surgery
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• 제42권1호
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• pp.20-27
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• 2015

Background Hypertrophic scars and keloids are associated with abnormal levels of growth factors. Silicone gel sheets are effective in treating and preventing hypertrophic scars and keloids. There has been no report on the change in growth factors in the scar tissue following the use of silicone gel sheeting for scar prevention. A prospective controlled trial was performed to evaluate whether growth factors are altered by the application of a silicone gel sheet on a fresh surgical scar. Methods Four of seven enrolled patients completed the study. Transforming growth factor (TGF)-${\beta}1$, platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) were investigated immunohistochemically in biopsies taken from five scars at 4 months following surgery. Results In both the epidermis and the dermis, the expression of TGF-${\beta}1$ (P=0.042 and P=0.042) and PDGF (P=0.043 and P=0.042) was significantly lower in the case of silicone gel sheet-treated scars than in the case of untreated scars. The expression of bFGF in the dermis was significantly higher in the case of silicone gel sheet-treated scars than in the case of untreated scars (P=0.042), but in the epidermis, the expression of bFGF showed no significant difference between the groups (P=0.655). Conclusions The levels of TGF-${\beta}1$, PDGF, and bFGF are altered by the silicone gel sheet treatment, which might be one of the mechanisms of action in scar prevention.

• Journal of Acupuncture Research
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• 제36권2호
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• pp.92-99
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• 2019

Background: This study was conducted to evaluate the effects of pharmacopuncture and dermal application of Sebalgukhwa-san extracts on hair growth in an alopecia mouse model. Methods: Twenty-one C57BL/6 mice were divided into 3 groups; control group-normal saline injection or vehicle solution application, positive control group-minoxidil (MNXD), experimental group-pharmacopuncture and applied Sebalgukhwa-san (SGS) extract. The effects of the treatment on hair growth, were determined through photographs, and phototrichogram analysis by folliscope. Hair follicle morphometry by hematoxylin-eosin staining was performed, and hair growth-related protein expression of vascular endothelial growth factor, insulin like growth factor-1, and transforming growth factor-beta 1 were monitored by Western blotting. Serum levels of aspartate aminotransferase and alanine aminotransferase were measured for liver function test. Results: Body weight increased consistently in all groups. Hair growth was improved in the MNXD and SGS groups compared with the control. Hair density and thickness improved statistically significantly in the MNXD and SGS groups compared with the control p < 0.05. The number of hair follicles improved in the MNXD and SGS groups compared with the control but the size did not. The expression of vascular endothelial growth factor and insulin like growth factor-1 increased, and there was a decrease in the expression of transforming growth factor-beta 1 in the MNXD and SGS groups compared with the control, however, there was no significant difference. Sebalgukhwa-san treatment had no toxicity in liver function tests. Conclusion: Pharmacopuncture and dermal application of Sebalgukhwa-san extract may be therapeutically beneficial for the treatment of alopecia.

• International Journal of Molecular Medicine
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• 제44권2호
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• pp.491-502
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• 2019

Although the migration of hepatic stellate cells (HSCs) is important for hepatic fibrosis, the regulation of this migration is poorly understood. Notably, transforming growth factor (TGF)-β1 induces monocyte migration to sites of injury or inflammation during the early phase, but inhibits cell migration during the late phase. In the present study, the role of transforming protein RhoA signaling in TGF-β1-induced HSC migration was investigated. TGF-β1 was found to increase the protein and mRNA levels of smooth muscle actin and collagen type I in HSC-T6 cells. The level of RhoA-GTP in TGF-β1-stimulated cells was significantly higher than that in control cells. Furthermore, the phosphorylation of cofilin and formation of filamentous actin (F-actin) were more marked in TGF-β1-stimulated cells than in control cells. Additionally, TGF-β1 induced the activation of nuclear factor-κB, and the expression of extracellular matrix proteins and several cytokines in HSC-T6 cells. The active form of Rap1 (Rap1 V12) suppressed RhoA-GTP levels, whereas the dominant-negative form of Rap1 (Rap1 N17) augmented RhoA-GTP levels. Therefore, the data confirmed that Rap1 regulated the activation of RhoA in TGF-β1-stimulated HSC-T6 cells. These findings suggest that TGF-β1 regulates Rap1, resulting in the suppression of RhoA, activation of and formation of F-actin during the migration of HSCs.