• Title/Summary/Keyword: Up-Regulation

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Effect of ganglioside GD3 synthase gene expression on VSMC proliferation via ERK1/2 pathway, cell cycle progression and MMP-9 expression

  • Lee, Young-Choon;Kim, Cheorl-Ho
    • Proceedings of the Korean Society of Plant Biotechnology Conference
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    • 2004.10a
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    • pp.81-90
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    • 2004
  • Sialic acid containing glycosphingolipids (gangliosides) have been implicated in the regulation of various biological phenomena such as atherosclerosis. Recent report suggeststhat exogenously supplied disialoganglioside (GD3) serves a dual role in vascular smooth muscle cells (VSMC) proliferation and apoptosis. However, the role of the GD3 synthase gene in VSMC responses has not yet been elucidated. To determine whether a ganglioside is able to modulate VSMC growth. the effect of overexpression of the GD3 synthase gene on DNA synthesis was examined. The results show that the overexpression of this gene has a potent inhibitory effect on DNA synthesis and ERK phosphorylation in cultured VSMC in the presence of PDGF. The suppression of the GD3 synthase gene was correlated with the down-regulation of cyclinE/CDK2. the up-regulation of the CDK inhibitor p21 and blocking of the p27 inhibition,whereas up-regulation of p53 as the result of GD3 synthase gene expression was not observed. Consistently, blockade of GD3 function with anti-GD3 antibody reversed VSMC proliferation and cell cycle proteins. The expression of the CD3 synthase gene also led to the inhibition of TNF--induced matrix metalloproteinase-9 (MMP-9) expression in VSMC as determined by zymography and immunoblot. Furthermore, GD3 synthase gene expression strongly decreased MMP-9 promoteractivlty in response to TNF-. This inhibition was characterized by the down-regulation of MMP-9,which was Iranscriptionally regulated at NF-B and activation protein-1 (AP-1) sites in the MMP-9promoter Finally, the overexpression of MMP-9 in GD3 synthase transfectant cells rescued VSMC proliferation. However MMP-2 overexpression was not affected the cell proliferation. These findings suggest that the fl13 synthase gene represents a physiological modulator of VSMC responses that may contribute to plaque instability in atherosclerosis.

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he Influence of Posttraumatic Stress on Suicidal Ideation in Firefighters : Cognitive Emotion Regulation as a Moderator (소방공무원의 외상 후 스트레스가 자살생각에 미치는 영향 - 인지적 정서조절의 조절효과-)

  • Kim, Sung-Jung;Yook, Sung-Pil
    • Fire Science and Engineering
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    • v.32 no.2
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    • pp.92-101
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    • 2018
  • This study investigated the impact of post-traumatic stress of the fire-fighting officers who are exposed to traumatic events repeatedly on suicide and attempted to verify the moderating effect of cognitive emotion regulation in the relationship between post-traumatic stress and suicidal ideation. For this investigation, this study measured Post-traumatic stress Diagnostic Scale, Korean Beck scale for Suicidal Ideation, Cognitive Emotion Regulation Questionnaire. The research results are as follows. First, Post-traumatic stress, suicidal ideation, adaptive cognitive emotion regulation, and maladaptive cognitive emotion regulation were correlated. second, A hierarchical regression analysis was conducted in order to examine the moderating effect of cognitive emotion regulation in the relationship between post-traumatic stress and suicidal ideation, and as a result, it was found that a sub-factor of cognitive emotion regulation, adaptive cognitive emotion regulation had a moderating effect in a group of persons with low post-traumatic stress, while maladaptive cognitive emotion regulation had a moderating effect in a group of persons with high post-traumatic stress. These results, this study discussed the necessity of follow-up studies, in addition to its academic and clinical implications.

The Analysis of Environmental Protection Sector and Regulation Resistance -A Study on Pyeongchang- (환경규제 지역과 규제저항 분석 - 평창을 사례로 -)

  • Bae, Sun-Hak
    • Journal of the Korean Geographical Society
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    • v.41 no.6 s.117
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    • pp.701-713
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    • 2006
  • This study considers the case when a district with a high development possibility is set up as a regulation region. Initial assumption is that there would be regulation resistance in and around the regulation region. Pyeongchang is taken as a study areas, performing necessary analysis of environment regulation and regulation resistance based upon spatial analysis with the use of GIS. The research proceeding steps are as follows. After examining Pyeongchang present environment regulation state, environment regulation map is constructed, and classification of Pyeongchang's relatively development possibility level map is made. Using this regulation map and development possibility level map, relative regulation resistance level is measured. The results that the rates of Pyeongchang environment regulation region in its present state was higher than Namhan river basin's regulation region rates. Also, overlapping a high development possibility level region with an environment regulation region, the analysis results give reasons to expect high level of regulation resistance in Doam-myeon and Jinbu-myeon in small town units. The analysis of Pyeongchang new buildings locations with regard to environment regulation showed intensive distribution in the regulation region with high development possibility level and adjacent areas (about 66% of new buildings are distributed within 500m range from regulation region). Such results show that the local administration and existing environment regulation policy, not capable of offering direct benefit to the population, are having immanent problems in environment sustainable development and connected with it environment harm causation.

Expression of Fra1 and Fra2 Genes are regulated by Estrogen in the Mouse Uterus (생쥐자궁에서 에스트로겐에 의해 조절되는 Fra1과 Fra2 유전자의 발현양상)

  • Lee, Ji-Yoon;Hong, Seok-Ho;Nah, Hee-Young;Kim, Sung-Hoon;Chae, Hee-Dong;Kim, Chung-Hoon;Kang, Byung-Moon;Kim, Moon-Kyoo
    • Clinical and Experimental Reproductive Medicine
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    • v.30 no.4
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    • pp.309-316
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    • 2003
  • 연구목적: 스테로이드 계통의 에스트로겐 호르몬은 막 수용체와 결합하고 DNA에 부착되어, 자궁조직에서 발현되는 많은 유전자들의 발현 양상을 조절하는 것으로 알려져 있다. 본 연구에서는 난소를 제거한 생쥐 모델을 이용하여 에스트로겐에 의해 조절되는 전사 관련 유전자(transcription factor)들을 동정하고, early up-regulation gene으로 확인된 Fos related antigen (Fra1과 Fra2) 유전자의 발현 양상을 RT-PCR과 면역염색방법으로 살펴보았다. 연구재료 및 방법: 난소 절제술을 시행한 생쥐에 에스트로겐을 피하주사하고 2, 4, 6, 12시간 간격으로 자궁조직을 적출하였다. 대조군으로는 sesame oil만을 주사한 후 2시간째에 수획한 자궁조직을 사용하였으며, 시간대별로 채취한 자궁조직(n=4)에서 RT-PCR을 수행하였다. RT-PCR을 통해 early response gene으로 확인된 Fra1과 Fra2에 대한 에스트로겐의 영향을 살펴보기 위해 estrogen receptor antagonist인 ICI 182, 780을 주사하여 유전자 발현 양상의 변화를 살펴보았다. 또한, 자궁조직내에서의 단백질 발현 부위를 관찰하기 위해 면역조직화학염색을 실시하였다. 결 과: 생쥐 자궁조직에서 에스트로겐에 의해 발현 양상의 변화가 확인된 유전자는 early up-regulation genes (CREB2, Fra-1, 2, GATA5), late up-regulation gene (E2F1), no response genes (CREB1, ATF1, GLI3, E2F3), down-regulation genes (GLI2, E2F5, GATA-2, 3, 6) 등으로 구분할 수 있었다. 그 중 early up-regulation genes에 해당하는 Fra1과 Fra2 유전자는 ICI 182, 780에 의해 그 발현이 유의하게 감소되는 것을 확인하였다(p < 0.01). 이들 단백질은 생쥐 자궁조직의 상피세포층, 기질층, 근육층에서 고루 발현되었으며, 특히 근육층에서 강한 염색정도를 관찰할 수 있었다. 결 론: 이상의 결과를 통해 Fra1과 Fra2 유전자의 발현은 에스트로겐에 의해 조절됨을 알 수 있었으며, 이들의 강한 발현이 자궁조직의 근육층에서 관찰되어 이들의 기능에 대한 연구가 필요할 것으로 생각된다.

Up-regulation of Matrix Metalloproteinase-9 in Smooth Muscle Cell Undergoing Death (사멸세포에서의 metalloproteinase-9의 작용)

  • Lee, Kyeong-Ah;Kim, Sun-Mi;Kim, Koan-Hoi
    • Journal of Life Science
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    • v.16 no.7 s.80
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    • pp.1229-1234
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    • 2006
  • This study investigated whether matrix metalloproteinases (MMPs) can be modified in apoptotic smooth muscle cell (SMC) using the SMC that undergoes apoptotic death by expressing Fas-associated death domain containing protein (FADD) when they are grown without tetracycline in culture medium. In the absence of tetracycline, FADD-SMC lost adherence and showed the fragmentation of the nuclei. In proportion to duration of tetracycline removal, phosphorylated form of p38 MAPK and of ERK increased, whereas phosphorylation of protein kinase B (PKB) was not changed very much in response to tetracycline The levels of cyclin A and cyclin D were also decreased in a time dependent manner. Up-regulation of MMP-9 expression and activity was observed when the SMC were grown without tetracycline. Immunoreactivity of MMP-9 was detected from both attached and floating FADD-SMCs grown without tetracycline. An inhibitor of MAPK kinase, PD098059, and an inhibitor of p38 MAPK, SB203580, inhibited the up-regulation of MMP-9. Treatment of the SMC with a synthetic MMP inhibitor, BB94, attenuated death occurring in the absence of tetracycline. These results indicate that SMC undergoing death is able to up-regulate MMP-9 and that the enzyme can affect cell viability.

Modulatory Effect of Diethylstilbestrol on CD29-Mediated Cell-cell Adhesion in Monocytic U937 Cells (Diethylstilbestrol의 단핵구의 세포간 유착과정 조절효과)

  • Kim, Byung-Hun;Cho, Jae-Youl
    • YAKHAK HOEJI
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    • v.52 no.2
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    • pp.111-116
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    • 2008
  • Diethylstilbestrol (DESB) is a synthetic estrogen not only that routinely prescribed, but also that known to be a teratogen. In this study, we found a novel pharmacological feature that DESB is able to positively modulate CD29 $({\beta}1-integrin)$ function. Thus, DESB up-regulated homotypic cell-cell adhesion of monocytic U937 cells mediated by CD29. However, DESB did not increase the surface level of CD29 and its binding activity to ligand (fibronectin), according to flow cytometric analysis and cell-fibronectin adhesion assay. Instead, the DESB-mediated up-regulation of cell-cell adhesion was blocked by several signaling enzyme inhibitors. Treatment of U0126 [an extracellular signal-regulated kinase (ERK) inhibitor], SB20358 (a p38 inhibitor) or Rp-8-pCPT-cGMP (a protein kinase G inhibitor) clearly inhibited DESB-mediated up-regulation of cell-cell adhesion induced by CD29. However, estrogen receptor antagonist ICI 182,780 failed to abrogate DESB effect. Therefore, our data suggest that DESB may up-regulate CD29-mediated cell-cell adhesion via modulating intracellular signaling enzymes such as ERK, PKG, and p38, independent of estrogen receptor function.

The microRNA expression profiles of mouse mesenchymal stem cell during chondrogenic differentiation

  • Yang, Bo;Guo, Hongfeng;Zhang, Yulan;Dong, Shiwu;Ying, Dajun
    • BMB Reports
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    • v.44 no.1
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    • pp.28-33
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    • 2011
  • MicroRNAs are potential key regulators in mesenchymal stem cells chondrogenic differentiation. However, there were few reports about the accurate effects of miRNAs on chondrogenic differentiation. To investigate the mechanisms of miRNAs-mediated regulation during the process, we performed miRNAs microarray in MSCs at four different stages of TGF-${\beta}3$-induced chondrogenic differentiation. We observed that eight miRNAs were significantly up-regulated and five miRNAs were downregulated. Interestingly, we found two miRNAs clusters, miR-143/145 and miR-132/212, kept on down-regulation in the process. Using bioinformatics approaches, we analyzed the target genes of these differentially expressed miRNAs and found a series of them correlated with the process of chondrogenesis. Furthermore, the qPCR results showed that the up-regulated (or down-regulated) expression of miRNAs were inversely associated with the expression of predicted target genes. Our results first revealed the expression profiles of miRNAs in chondrogenic differentiation of MSCs and provided a new insight on complicated regulation mechanisms of chondrogenesis.

Up-Regulation of $p27^{Kip1}$ Protects hES Cells from Differentiation-Associated and Caspase 3-Dependent Apoptosis

  • Park, So-Hyun;Kim, Min Kyoung;Lee, Chul-Hoon
    • Journal of Microbiology and Biotechnology
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    • v.22 no.12
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    • pp.1790-1794
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    • 2012
  • Recently, it has been suggested that $p27^{Kip1}$, the cell cycle regulatory protein, plays a pivotal role in the progression of normal differentiation in murine embryonic stem (mES) cells. In the current study, we investigated the role of $p27^{Kip1}$ in the regulation of differentiation and apoptotic induction using Western blotting, quantitative real-time RT-PCR, and small interfering RNA (siRNA) assays and confocal laser scanning microscopic analysis of H9 human ES (hES) cells and H9-derived embryoid bodies (EBs) grown for 10 ($EB_{10}$) and 20 days ($EB_{20}$). Our results demonstrate that the proteins $p27^{Kip1}$ and cyclin D3 are strongly associated with cellular differentiation, and, for the first time, show that up-regulation of $p27^{Kip1}$ protects hES cells from inducing differentiation-associated and caspase 3-dependent apoptosis.

The Effect of Regulation in the New Industry on the Business Performance (신산업 분야의 규제 도입이 기업 성과에 미치는 영향)

  • Lee, Sang-Kyu;Kim, Soo-Dong;Kim, Soo-Hyun
    • The Journal of the Korea Contents Association
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    • v.16 no.11
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    • pp.179-187
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    • 2016
  • Many research works have been done in the field of the relationship between regulations and business activities. In general, the relationship is negative, so government took a regulation relaxation policy for some period. However, recently, the better regulation concept is more emphasized than the regulation relaxation. In particular, as the new industry comes to appear, we need to analyze the effect of regulations in the new industry to the business activities, and set up the regulation advancement policy. In this paper, the effect of regulations in the new industry on business activities and performance was analyzed and implications for better regulation policy was derived. According to the results, the effect was different according to the firm's size and the degree of integration in R&D. Therefore we need some consideration of the firm's size and the degree of integration in R&D for establishing the regulatory policies.

Exploratory Study on Consumer Attitude toward the SSM Regulation Law (유통산업발전법 개정에 따른 소비자 반응 탐색연구)

  • Nam, Se-Hyun;Cho, Yoon-Ki;Yoo, Jeong-Seok;Kim, Dong-Tae
    • Journal of Distribution Science
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    • v.11 no.10
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    • pp.47-53
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    • 2013
  • Purpose - Six months have passed since the amendment of the SSM regulation law; however, as yet, there is no confirmed research or report on the effects of this amendment, which are indefinite. Further, there have been no attempts to study the effects of the SSM regulation law from the consumers' viewpoint, which is important because consumers are the main agents that are greatly influenced by the amendment law. Therefore, this study aims to investigate the consumers' attitude toward the SSM regulation law as well as the effects of the SSM regulation law on the changes in purchase behavior. Research design, data, and methodology - This study was initiated from four research problems that are linked to consumer reaction to the SSM regulation law. Research problem 1: What is the consumers' reaction (perception, attitude, and perceived fairness) to the SSM regulation law? Research problem 2: How do the consumers' reactions to the SSM regulation law differ by consumers' characteristics? Research problem 3: Could the SSM regulation law change a consumer's purchase behavior? Research problem 4: Is it necessary to amend the SSM regulation law? This study collected the data through the interview and survey of housewives for the purpose of solving the research problems. The interview was conducted as a pilot study for the field survey. We interviewed three housewives, who were: an employed housewife, a full-time homemaker, and a manager of a housewife club, respectively. We then conducted a field survey of 232 housewives who were housewife club members or elementary school parents in Chunghcheong-do. Results - We verified the reliability and validity of the data, and analyzed it to solve the research problems. The main findings of this study were as follows. First, consumers still have a positive attitude toward large discount chains and SSM, which has been the case since the law was introduced. Second, perceived risk of consumers associated with traditional markets and small neighborhood shops was low. Third, consumers think that amendments of the SSM regulation law are important, and they positively assess the satisfaction, necessity, and propriety of the law. Fourth, although the SSM regulation law caused inconvenience to consumers, this law did not have any influence on the usage frequency and the use-behavior of large discount chains. Finally, consumers reacted very negatively to the toughening up of the SSM regulation law. Conclusions - In short, consumers still have a positive attitude toward the SSM regulation law. However, this act did not have any influence on the use-behavior of large discount chains (General Super Market). Thus, policy making authorities require active communication and promotions to enhance the effect of the SSM regulation law. This study was of the nature of exploratory research, which did not focus on hypothesis testing, but on finding solutions to the research problems. Therefore, this study is no more than a simple data analysis. Future studies should attempt to investigate the actual effects of the SSM regulation law, on the basis of sufficient literature review and real sales data.