• 제목/요약/키워드: Transforming growth factor-${\beta}$

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Inhibitors of DNA methylation support TGF-β1-induced IL11 expression in gingival fibroblasts

  • Sufaru, Irina-Georgeta;Beikircher, Gabriel;Weinhaeusel, Andreas;Gruber, Reinhard
    • Journal of Periodontal and Implant Science
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    • 제47권2호
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    • pp.66-76
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    • 2017
  • Purpose: Oral wound healing requires gingival fibroblasts to respond to local growth factors. Epigenetic silencing through DNA methylation can potentially decrease the responsiveness of gingival fibroblasts to local growth factors. In this study, our aim was to determine whether the inhibition of DNA methylation sensitized gingival fibroblasts to transforming growth factor-${\beta}1$ (TGF-${\beta}1$). Methods: Gingival fibroblasts were exposed to 5-aza-2'-deoxycytidine (5-aza), a clinically approved demethylating agent, before stimulation with TGF-${\beta}1$. Gene expression changes were evaluated using quantitative polymerase chain reaction (PCR) analysis. DNA methylation was detected by methylation-sensitive restriction enzymes and PCR amplification. Results: We found that 5-aza enhanced TGF-${\beta}1$-induced interleukin-11 (IL11) expression in gingival fibroblasts 2.37-fold (P=0.008). 5-aza had no significant effects on the expression of proteoglycan 4 (PRG4) and NADPH oxidase 4 (NOX4). Consistent with this, 5-aza caused demethylation of the IL11 gene commonly next to a guanosine (CpG) island in gingival fibroblasts. The TGF-${\beta}$ type I receptor kinase inhibitor SB431542 impeded the changes in IL11 expression, indicating that the effects of 5-aza require TGF-${\beta}$ signaling. 5-aza moderately increased the expression of TGF-${\beta}$ type II receptor (1.40-fold; P=0.009), possibly enhancing the responsiveness of fibroblasts to TGF-${\beta}1$. As part of the feedback response, 5-aza increased the expression of the DNA methyltransferases 1 (DNMT1) (P=0.005) and DNMT3B (P=0.002), which are enzymes responsible for gene methylation. Conclusions: These in vitro data suggest that the inhibition of DNA methylation by 5-aza supports TGF-${\beta}$-induced IL11 expression in gingival fibroblasts.

Role of the transforming growth factor (TGF)-β1 and TGF-β1 signaling pathway on the pathophysiology of respiratory pneumococcal infections

  • Andrade, Maria Jose;Lim, Jae Hyang
    • Journal of Yeungnam Medical Science
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    • 제34권2호
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    • pp.149-160
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    • 2017
  • Streptococcus pneumoniae, pneumococcus, is the most common cause of community-acquired pneumonia (CAP). CAP is an important infectious disease with high morbidity and mortality, and it is still one of the leading causes of death worldwide. Many genetic factors of the host and various environmental factors surrounding it have been studied as important determinants of the pathophysiology and outcomes of pneumococcal infections. Various cytokines, including transforming growth factor $(TGF)-{\beta}1$, are involved in different stages of the progression of pneumococcal infection. $TGF-{\beta}1$ is a cytokine that regulates a wide range of cellular and physiological functions, including immune and inflammatory responses. This cytokine has long been known as an anti-inflammatory cytokine that is critical to preventing the progression of an acute infection to a chronic condition. On the other hand, recent studies have unveiled the diverse roles of $TGF-{\beta}1$ on different stages of pneumococcal infections other than mitigating inflammation. This review summarizes the recent findings of the role of $TGF-{\beta}1$ on the pathophysiology of pneumococcal infections, which is fundamental to developing novel therapeutic strategies for such infections in immune-compromised patients.

세균 독소를 작용시킨 섬유아 세포에서 Transforming Growth Factor-${\beta}_1$의 생성 (PRODUCTION OF TRANSFORMING GROWTH FACTOR-${\beta}_1$ IN HUMAN FIBROBLASTS INDUCED WITH BACTERIAL TOXINS)

  • 이성근;김광혁
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제26권4호
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    • pp.345-354
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    • 2000
  • TGF-${\beta}_1$ is a potent chemotactic factor for inflammatory cells and fibroblasts. It also stimulates the celluar source and components of extracellular matrix and the production of proteinase inhibitors. Collectively, these biologic activities lead to the accumulation and stabilization of the nascent matrix, which is vital to wound healing. The objective of this study is to investigate production of TGF-${\beta}_1$ in vitro fibroblast culture in the presence of Staphylococcus enterotoxin B(SEB) and/or lipopolysaccharide(LPS) and to elucidate the role of TGF-${\beta}_1$ which may be responsible for wound healing. The fibroblasts were originated from facial dermis and hypertrophic scar in 26 year-old male patient. In the presence of LPS($0.01{\mu}g$, $0.1{\mu}g$, $1.0{\mu}g$), SEB($0.01{\mu}g$, $0.1{\mu}g$, $1.0{\mu}g$) respectively, cells($5{\times}10^3ml$) were cultivated in vitro. At 1, 3, and 5 days after incubation, cells were counted. Also, cells($2.5{\times}10^5ml$) were cultivated in EMEM with LPS(0.01, 0.1 and $1.0{\mu}g$), SEB(0.01, 0.1 and $1.0{\mu}g$) respectively and LPS($0.1{\mu}g$) and SEB($0.1{\mu}g$) in combination for 24, 48, and 72 hours respectively. Culture supernatants were harvested at 1, 2, and 3 days after incubation period and triplicate culture supernatants were pooled and TGF-${\beta}_1$ was assayed in duplicate. The results were as follows. 1. In facial dermal fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell proliferation occurred very significantly at 1 day after incubation, compared with the control. In SEB exposure, the production of TGF-${\beta}_1$ was decreased very significantly at 1 day after incubation, compared with the control. However, in LPS, SEB and LPS exposure, the production of TGF-${\beta}_1$ was increased very significantly at 1 day after incubation, compared with the control. 2. In hypertrophic scar fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell proliferation did not occur at 1 day after incubation, compared with the control. In SEB and LPS exposure in combination, the production of TGF-${\beta}_1$ was increased very significantly at 1 day after incubation, compared with the control. However, the production of TGF-${\beta}_1$ did not occur in SEB and LPS exposure respectively. In conclusion, the concentration of bacterial toxins and the incubation period correlated with cell proliferation and production of TGF-${\beta}_1$ very significantly and both fibroblasts have different phenotype each other in this regard. This data suggest that the significant production of TGF-${\beta}_1$ may develope abnormal wound healing associated with tissue fibroproliferative disorder, such as hypertrophic scar and keloid formation.

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Induction of transforming growth factor-beta 1 by androgen is mediated by reactive oxygen species in hair follicle dermal papilla cells

  • Shin, Hyoseung;Yoo, Hyeon Gyeong;Inui, Shigeki;Itami, Satoshi;Kim, In Gyu;Cho, A-Ri;Lee, Dong Hun;Park, Won Seok;Kwon, Ohsang;Cho, Kwang Hyun;Won, Chong Hyun
    • BMB Reports
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    • 제46권9호
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    • pp.460-464
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    • 2013
  • The progression of androgenetic alopecia is closely related to androgen-inducible transforming growth factor (TGF)-${\beta}1$ secretion by hair follicle dermal papilla cells (DPCs) in bald scalp. Physiological levels of androgen exposure were reported to increase reactive oxygen species (ROS) generation. In this study, rat vibrissae dermal papilla cells (DP-6) transfected with androgen receptor showed increased ROS production following androgen treatment. We confirmed that TGF-${\beta}1$ secretion is increased by androgen treatment in DP-6, whereas androgen-inducible TGF-${\beta}1$ was significantly suppressed by the ROSscavenger, N-acetyl cysteine. Therefore, we suggest that induction of TGF-${\beta}1$ by androgen is mediated by ROS in hair follicle DPCs.

돼지난자의 체외성숙시 Transforming Growth Factor$\beta$와 난구세포의 상호작용 (Interaction between Transforming Growth Factor $\beta$ and Cumulus Cells during In Vitro Maturation in Porcine Oocytes)

  • 신명균;조재원;정희태;양부근;김정익;박춘근
    • 한국가축번식학회지
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    • 제22권1호
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    • pp.73-80
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    • 1998
  • 본 연구는 돼지난자의 체외성숙에 미치는 transforming growth factor $\beta$(TGF $\beta$)와 난수세포의 역할에 대하여 검토하였다. 난자의 체외성숙시 TGF $\beta$를 여러 농도에서 첨가한 경우 metaphase II로 성숙한 난자의 비율은 52~69%로 유의적인 차이는 나타내지 않았다. 성숙배양 24시간에서 난구세포의 유무에 관계없이 TGF $\beta$가 무첨가된 배양액 내에서는 성숙된 난자가 관찰되지 않았으나 TGF $\beta$첨가(5 및 4%)의 경우 성숙난자가 관찰되었다. 그러나, 성숙배양 48시간후 난자의 성숙율은 난구세포가 부착되어 있는 경우 TGF $\beta$첨가(70%)가 무첨가(52%)에 비해 높았으며, 난구세포를 세포를 제거한 경우 (35 및 26%)에 비해 유의적으로 높은 성숙율을 나타냈다(P<0.05). 한편, 나구세포가 부착된 난자의 성숙배양시 TGF $\beta$의 첨가시기에 의한 성숙율(54~71%)에는 큰 차이가 없었으나, 난구세포를 제거한 경우 전반기(59%) 또는 후반기(57%) 24시간 동안 TGF $\beta$를 첨가한 경우 48시간 동안 계속하여 첨가(27%) 또는 무첨가(38%)에 비하여 유의적으로 높은 성숙을 나타냈다(P<0.05). 이와 같은 결과는 난구세포가 돼지난자의 체외성숙시 필수적이지만, TGF $\beta$는 난구세포를 제거한 경우 난자의 성숙에 계속적인 역할을 하지 않는 것으로 추측된다.

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영지의 ${\beta}$-glucan성 다당류에 의해 활성화된 흰쥐 간내 Kupffer 세포의 NO, TNF-${\alpha}$ 및 TGF-${\beta}$ 형성 (Nitric Oxide, TNF-${\alpha}$ and TGF-${\beta}$ Formation of Rat Kupffer Cell Activated by the ${\beta}$-Glucan from Ganoderma lucidum)

  • 한만덕;이준우;정훈;김용석;나수정;윤경하
    • 한국미생물·생명공학회지
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    • 제27권1호
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    • pp.28-34
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    • 1999
  • Ganoderan (GAN), an immunomodulating ${\beta}$-glucan from mushroom Ganoderma lucidum, was evaluated for its ability to induce formation of nitric oxide (NO), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) and transforming growth factor (TGF-${\beta}$) from rat Kupffer cell in vitro. Hepatic macrophages activated by GAN significantly elevated concentration of NO and TNF-${\alpha}$ in cultured medium, but not significantly elevated that of TGF-${\beta}$. GAN-activated Kupffer cells secrete 14.9${\mu}$M (p<0.01) of NO and 2619.5${\rho}$g/ml (p<0.01) of TNF-${\alpha}$after 36hr of incubation at 37$^{\circ}C$. The results revealed that GAN enhanced 4-fold production of NO and 19 fold formation of TNF-${\alpha}$ compared to the control. The proliferation of GAN-activated Kupffer cells was inhibited as compared with its negative control. Comparing the activity among glucans derived from microorganisms, highly branched zymosan, glucomannan from Saccharomyces cerevisiae, significantly increased TNF-${\alpha}$ and NO production. These results indicate that the ${\beta}$-glucan from G. lucidum activates rat Kupffer cell and secretes NO and TNF-${\alpha}$. It also suggest that rat Kupffer cell posses certain receptor for ${\beta}$-anomeric glucan.

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Phamacopuncture and Dermal Application of Sebalgukhwa-san: Effects on Hair Growth in a Mouse Model of Alopecia

  • Ji, Min Jung;Lim, Seong Chul;Kim, Jae Soo;Lee, Hyun Jong;Lee, Yun Kyu
    • 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.

Mineral trioxide aggregate (MTA)가 치주인대 섬유아세포에서 분비되는 cytokine과 성장인자 TGF-β1, FGF-2 발현에 미치는 영향 (The Effect of Mineral Trioxide Aggregate on the Production of Growth Factors and Cytokine by Human Periodontal Ligament Fibroblasts)

  • 권지윤;임성삼;백승호;배광식;강명회;이우철
    • 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.

TGF-$\alpha$, -$\beta$$_1$, and bFGF mRNA Expression of Lens Epithelial Cells in Senile and Diabetic Cataract

  • Hwang, Bum-Noon;Her, Jun
    • 대한의생명과학회지
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    • 제8권3호
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    • pp.127-135
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    • 2002
  • Anterior subcapsular cataract was developed by opacification with transdifferentiation and abnormal proliferation of lens epithelial cells (LECs) and pathological accumulation of extracellular matrix (ECM). After-cataract also be caused by a similar transdifferentiation of LECs remaining after surgery and the accompanying increase of ECM deposits. It is blown that prostaglandin E2 and cytokine, such as TGF-$\beta$, bFGF, and IL-1, were associated with abnormal proliferation and transdifferentiation of LECs. The aim of this study was to detect the expression of transforming growth factor-$\alpha$ (TGF-$\alpha$), transforming growth factor-$\beta_1$(TGF-$\beta_1$) and basic fibroblast growth factor (bFGF) in LECs of senile and diabetic cataract. The expressions of these growth factors in lens epithelial cells were determined. The sample for growth factor determination were collected in senile cataract patients without metabolic disorder, especially diabetes mellitus and diabetic cataract patients. The mRNA expression of growth factors was detected by semi-quantitative reverse transcription - polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Statistics were analysed using Wilcoxon rank sum test. Semi-quantitative RT-PCR/southern analysis of RNA obtained from thirty surgical specimens demonstrated that the level of mRNA expression of TGF-$\alpha$, -$\beta_1$ and bFGF was increased in diabetic cataract lens tissues compared with senile cataract specimens but non-significant, bFGF and TGF-$\beta_1$ mRNA expression were detected in most patients, expression level of TGF-$\beta_1$ was most high on the basis of normal ocular concentration. Detection rate of TGF-$\alpha$ in diabetic cataract was 1.5 fold higher than in senile cataract (P=0.098). TGF-$\alpha$, TGF-$\beta_1$, and bFGF mRNA expression of LECs were detected in senile and diabetic cataract. In both patient groups, expression level of TGF-$\beta_1$, mRNA was high, so We suggest TGF-$\beta_1$ strong influence in development of senile cataract and of diabetic cataract also. TGF-$\alpha$ expression level was similar but more frequently detected in diabetic cataract than in senile cataract. In conclusion, TGF-$\alpha$ may be associated with early development of diabetic cataract.

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