창상조절인자들이 창상수축에 미치는 영향:FPCL model을 이용한 실험적 방법

조을제,남성한,박준석,김점용,이호남,김동현 大韓成形外科學會 1999 Archives of Plastic Surgery Vol.26 No.5

Many investigators have reported that collagen gel contraction reflects the mechanism of wound contraction. In 1995, Tsai et al. reported that hypertrophic scar-derived fibroblasts in a connective tissue model possessed the greatest contraction potency when compared with those of normal skin and normal oral mucosa-derived CTMs. In this study, we studied the effect of collagen gel contraction by growth factors such as epidermal growth factor, platelet-derived growth factor, transforming growth factor-β1, and transforming growth factor-β3, Skin fibroblasts used in this study were obtained from the explant of rat skin culture. Fibroblasts were cultured in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum. Growth factors were added per FPCL in the desired concentrations and we measured the collagen gel diameters in growth factor-treated FPCL on day 1,2,3, and 4 respectively after starting incubation. We examined the effects of EGF, PDGF, TGF-β₁, TGF-β₃ and the effects of combinations of TGF-β₁+ EGF, TGF-β₁+ PDGF, and TGF-β₁+ TGF-β₃ to contract a collagen gel. EGF has little influence on collagen gel contraction. TGF-β₁ and TGF-β₃ increase the collagen contraction. TGF-β₁ enhanced the contractility of collagen gel according to the concentrations. While TGF-β₃ alone had stimulatory contraction effects at low dose, high doses of TGF-β₃ decreased the potency of collagen gel contraction. A combination of TGF-β₁ and EGF minimally decrease TGF-β₁ activity. A combination of TGF-β₁and PDGF had an effect similar to TGF-β₁ activity. A combination of TGF-β₁ and TGF-β₃ decreased TGF-β₁ activity. According to reports that FPCL contraction is equivalent to the process of wound contraction, growth factors which enhance gel contraction may be related to wound contraction and wound healing. TGF-β₁ is reported to enhance scar formation in fetal wound. EGF accelerates wound healing and inhibits the promotion of hypertrophic scar formation. Compared to the effect of collagen gel contraction in this study, the combination of TGF-β₁ and TGF-β₃ that inhibited the promotion of collagen gel contraction are thought to diminish the formation of scar tissue. As well, EGF that has not enhanced collagen gel contraction is thought to diminish the production of scar tissue. We will study the interactive effects of TGF-β₃, EGF and TGF-β₁ on the contraction of collagen gels in the future.

신세포암에서 Transforming Growth Factor-β1과 수용기 Ⅰ, Ⅱ, Ⅲ의 발현 변화

강상수,민경대,정승일,김세연,오봉렬,류수방,박양일 全南大醫大 2000 전남의대학술지 Vol.36 No.4

Expression of angiogenin, TGF-β, VEGF, APEX and TNF-α in oral squamous cell carcinoma

Ho-Sun Lee,Kyoung-Won Kim,Wun-Jae Kim 대한구강악안면외과학회 2006 대한구강악안면외과학회지 Vol.32 No.1

Purpose: The purpose of this study was to verify that the expressions of angiogenin, transforming growth factor-beta(TGF-β), vascular endothelial growth factor(VEGF), human apurinic/apyrimidinic endonuclease(APEX) and tumor necrosis factoralpha(TNF-α) were associated with the tumorigenesis of the oral squamous cell carcinoma(OSCC). Materials and Methods: Fifty-one samples of OSCC and fifteen normal oral mucosae were obtained to analyze the expression levels of above five factors. mRNA expressions were quantified by the quantitative competitive PCR(QC-PCR) method. After 2% agarose gel electrophoresis stained with ethidium bromide, the concentration of mRNA was calculated by a digital image analysis system. The expression levels of angiogenin, TGF-β, VEGF, APEX and TNF-αwere compared by unpaired Student’s ttests between cancer and normal tissues. We analyzed statistically to find the cut-off values that would be useful as diagnostic markers, and the linear regression analysis between every two factors of these five factors by SAS system. Results: All of these five factors (angiogenin: P<0.0037, TGF-β: P<0.0001, VEGF: P<0.0102, APEX: P<0.0023, TNF-α: P<0.0074) were significantly correlated with OSCC. In the analysis to find the cut-off values for the diagnosis, we could not find any value that had a reasonable sensitivity and specificity. In the linear regression analysis, there were correlations between angiogenin and TNF-α, TGF-βand VEGF, TGF-βand APEX, TGF-βand TNF-α, VEGF and APEX, VEGF and TNF-α, APEX and TNF-α. Conclusion: Our results suggest that not only angiogenin, TGF-β, VEGF, APEX and TNF-αare significantly associated with the tumorigenesis, but also the close relationship between these factors might enhance the tumorigenesis of OSCC. We can not find clinical availability for diagnosis.

Interleukin-18, transforming growth factor-β, and vascular endothelial growth factor gene polymorphisms and susceptibility to primary glomerulonephritis

Choi, H.-J.,Cho, J.-H.,Kim, J.-C.,Seo, H.-J.,Hyun, S.-H.,Kim, G.-H.,Choi, J.-Y.,Choi, H.-J.,Ryu, H.-M.,Cho, J.-H.,Park, S.-H.,Kim, Y.-L.,Han, S.,Kim, C.-D. Blackwell Publishing Ltd 2010 Tissue antigens Vol.76 No.4

<P>Several studies have showed an association of gene polymorphisms with the development of glomerulonephritis (GN). We investigated the effects of gene polymorphisms on the development of GN by analyzing polymorphisms in the interleukin (IL)-18, transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF) genes in Korean patients with primary GN. The study included 146 normal subjects (controls) and 100 patients diagnosed with primary GN by kidney biopsy. The gene polymorphisms A-607C and G-137C in <I>IL-18</I>, C-509T and T869C in <I>TGF-</I>β<I>1</I>, and C-2578A and C405G in <I>VEGF</I> were investigated in DNA extracted from peripheral blood. Significant differences were observed between the GN and control groups in the genotype and allele frequencies of A-607C <I>IL-18</I> and C405G <I>VEGF</I>. The frequencies of the <I>IL-18</I>−607CC genotype [<I>P</I> = 0.001, odds ratio (OR) = 2.473] and the <I>VEGF</I> 405GG genotype (<I>P</I> = 0.001, OR = 2.473) were significantly increased in the GN group. The combination of <I>IL-18</I>−607CC+ and <I>VEGF</I> 405GG+ genotypes had a higher risk for developing GN in comparison with the combination of <I>IL-18</I>−607CC− and <I>VEGF</I> 405GG− genotypes (<I>P</I> < 0.001, OR = 8.642). In the haplotype analysis of the <I>IL-18</I> gene, the CG haplotype was significantly more frequent in the GN group than the control group (61.5% <I>vs</I> 46.9%, <I>P</I> = 0.002). These results show that the −607CC genotype of the <I>IL-18</I> gene and the 405GG genotype of the <I>VEGF</I> gene are associated with susceptibility to and the development of primary GN.</P>

자궁근종과 자궁평활근에서 Transforming Growth Factor-β1의 표현 및 Collagen I, Ⅲ mRNA에 미치는 영향

이병석(BS Lee),박기현(KH Park),조동제(DJ Cho),이국(K Lee),김재욱(JU Kim),송찬호(CH Song),양우익(WI Yang) 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.9

Leiomyomas, which are the commonest pelvic tumors in women, are originated from myometrial cells. Although the exact initial pathophysiologic event of the leiomyoma is not known, recent evidences suggested that the effects of sex steroid hormones in the process of tumor growth are mediated by local production of growth factors including epidermal growth factor(EGF), in- sulin-like growth factor-I(IGF-I) and insulin-like growth factor-II(IGF-II). Recently, it was sugge- sted that transforming growth factor-β(TGF-β) may play a role for growing of leiomyomas. It was known that TGF-β increase the formation of extracellular matrix. And we examined TGF-β1 expression and tried to know the effect of TGF-β1 on the extracellular matrix, collagen I and III mRNA levels in cultured leiomyoma and myometrial cells. We found that immunoreactive TGF-β1 was expressed in myometriums and in leiomyomas. There was no difference at the intensity of immunostaining between two tissues. In northern blotting, there was no difference of TGF-β1 expression at the transcriptional level in both tissues. TGF-β1 increased the mRNA levels of collagen I in cultured myometrial and leiomyoma cells at the concentration of 1 ng/ml(p<0.05), 10 ng/ml(p<0.001). And TGF-β1 increased the mRNA levels of collagen III in cultured myo- metrial and leiomyoma cells at the concentration of 1 ng/ml (p<0.05), 10 ng/ml(p<0.05). Therefore, expressed TGF-β1 may stimulate the incorporation of collagen I and III into the extracellular matrix in myometriums and leiomyomas.

결정형 규산분진에 폭로된 섬유모세포의 자가증식 : Evaluation by H₂O₂and PDGF-AA 와 TGFβ

안병용,김경아,문제혁,정진숙,김은경,임영 대한산업의학회 2000 대한직업환경의학회지 Vol.12 No.2

Objectives : The aim of this study is to find out the activity of autoproliferation of rat fibroblast exposed to crystalline silica and the role of mediators secreted from rat fibroblast. Methods : The effect of α-quartz on production of growth factor (platelet-derived growth factor-AA and transforming growth factorβ) from rat fibroblasts were evaluated by ELISA and immunocytochemical analysis. Gene expression of these growth factors in rat fibrobast exposed to crystalline silica was evaluated by RT-PCR. Furthermore, fibroblast proliferation by culture supernatant of rat fibroblast was assayed by the neutral red test. Results : The amounts of H2O2 and growth factors synthesized in rat fibroblasts were significantly increased by the stimulation of crystalline silica (α-quartz) , which showed the dose-dependent manner to the concentration of α-quartz with the maximum response at the dosage of 100 ㎍/㎠. The result of RT-PCR demonstrated that α-quartz induced gene expression of PDGF-AA and TGFβ in rat fibroblast. We also found that supernatant of α-quartz-cocultured rat fibroblast induced a significant proliferation of fibroblast. Conclusion : Crystalline silica directly induce functional change In fibroblast such as increased release of reactive oxygen species and growth factors. The products of these functional change promote fibroblast proliferation via autocrine loop.

위암의 AFP, TGF-β, EGF 및 AAT에 대한 면역조직화학적 연구

정숙금,최환준,구자영,허만하 대한병리학회 1994 Journal of Pathology and Translational Medicine Vol.28 No.5

Synergistic Effect of Combined Growth Factors in Porcine Intervertebral Disc Degeneration

Cho, Hongsik,Lee, Sangmin,Park, Sang-Hyug,Huang, Jinsong,Hasty, Karen A.,Kim, Song-Ja Informa Healthcare 2013 Connective tissue research Vol.54 No.3

<P>Although intervertebral disc (IVD) degeneration is one of most common causes of morbidity, its etiology remains unclear. In healthy discs, the rates of synthesis and breakdown of the extracelluar matrix (ECM) are in equilibrium because of intricate regulation by growth factors and catabolic cytokines. Important among these physiologic growth factors are transforming growth factor-β (TGF-β1) and bone morphogenetic protein-2 (BMP-2). Disc degeneration is thought to be associated with a loss of this homeostasis between proteoglycan (PG) synthesis and cytokine-induced degradation leading to up-regulation of matrix metalloproteinases (MMP) families and down-regulation of extracelluar matrix production. Several strategies using biological agents have been attempted to manage IVD degeneration, improving the function and anabolic capabilities of IVD cells and inhibiting matrix degradation. The purpose of this study is to compare the effects of the anabolic cytokines BMP-2 and TGF-β1 with those of the catabolic cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) on porcine annulus fibrosus (AF). The results of this study show that the application of pro-inflammatory cytokines like tumor necrosis factor-α and interleukin-1β to normal annulus fibrosus cells leads to a significant increase in tissue levels of the degradative protease MMP-1. Treatment with a combination of minimum doses of both BMP-2 and TGF-β1 caused a greater decrease in MMP-1 and increase in aggrecan than either cytokine alone, suggesting a synergistic effect of the combined cytokines.</P>

Cinvited Review : Targeting the Transforming Growth Factor-β Signaling in Cancer Therapy

( Yhun Yhong Sheen ),( Min Jin Kim ),( Sang A Park ),( So Yeon Park ),( Jeong Seok Nam ) 한국응용약물학회 2013 Biomolecules & Therapeutics(구 응용약물학회지) Vol.21 No.5

TGF-β pathway is being extensively evaluated as a potential therapeutic target. The transforming growth factor-β (TGF-β) signaling pathway has the dual role in both tumor suppression and tumor promotion. To design cancer therapeutics successfully, it is important to understand TGF-β related functional contexts. This review discusses the molecular mechanism of the TGF-β pathway and describes the different ways of tumor suppression and promotion by TGF-β. In the last part of the review, the data on targeting TGF-β pathway for cancer treatment is assessed. The TGF-β inhibitors in pre-clinical studies, and Phase I and II clinical trials are updated.

Regulation of Tumor Immune Surveillance and Tumor Immune Subversion by TGF-β

Hae-Young Park,Lalage M Wakefield,신서자 대한면역학회 2009 Immune Network Vol.9 No.4

Transforming growth factor-β (TGF-β) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-β facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-β antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-β antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic CD8+ T cells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-β on T cells, which are differentiated into effector T cells or newly identified tumor- supporting T cells.