• Molecules and Cells
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• 제37권3호
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• pp.270-274
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• 2014

Lymphatic vessels are essential to regulate interstitial fluid homeostasis and diverse immune responses. A number of crucial factors, such as VEGFC, SOX18, PROX1, FOX2C, and GJC2, have been implicated in differentiation and/or maintenance of lymphatic endothelial cells (LECs). In humans, dysregulation of these genes is known to cause lymphedema, a debilitating condition which adversely impacts the quality of life of affected individuals. However, there are no currently available pharmacological treatments for lymphedema, necessitating identification of additional factors modulating lymphatic development and function which can be targeted for therapy. In this report, we investigate the function of genes associated with Bone Morphogenetic Protein (BMP) signaling in lymphatic development using zebrafish embryos. The knock-down of BMP type II receptors, Bmpr2a and Bmpr2b, and type I receptors, Alk3 and Alk3b, as well as SMAD5, an essential cellular mediator of BMP signaling, led to distinct lymphatic defects in developing zebrafish. Therefore, it appears that each constituent of the BMP signaling pathway may have a unique function during lymphatic development. Taken together, our data demonstrate that BMP signaling is essential for normal lymphatic vessel development in zebrafish.

• BMB Reports
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• 제52권7호
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• pp.451-456
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• 2019

NDRG1 has been reported to exert pivotal roles in tumor progression and metastasis via Wnt/${\beta}$-catenin signaling pathway. However, little is known about the role of NDRG3 in hepatocarcinogenesis despite its classification in the same subfamily of NDRG1. The present study was aimed to characterize the expression pattern and understand the biological roles of NDRG3 in hepatocarcinogenesis, as a means to exploit its therapeutic potential. It was observed that NDRG3 was up-regulated in HCC tissues and higher NDRG3 expression was associated with significantly shorter overall survival. Furthermore, a lower level of NDRG3 exhibited marked positive correlation with metastasis-free survival. In vitro and in vivo experiments revealed that knock-down of NDRG3 inhibits HCC metastasis and angiogenesis. We further demonstrated that activation of WNT/${\beta}$-catenin signaling and enhanced CSC-like properties were responsible for NDRG3-mediated promoting effect on HCC. In conclusion, the principal findings demonstrated that high NDRG3 expression facilitates HCC metastasis via regulating the turnover of ${\beta}$-catenin, as well as provides a potential therapeutic target for future therapeutic interventions.

• Molecules and Cells
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• 제42권1호
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• pp.67-78
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• 2019

Methylation of HBV cccDNA has been detected in vivo and in vitro; however, the mechanism and its effects on HBV replication remain unclear. HBx derived from a 1.2-mer HBV replicon upregulated protein levels and enzyme activities of DNA methyltransferase 1 (DNMT1), 3a, and 3b, resulting in methylation of the negative regulatory region (NRE) in cccDNA, while none of these effects were observed with an HBx-null mutant. The HBx-positive HBV cccDNA expressed higher levels of HBc and produced about 4-fold higher levels of HBV particles than those from the HBx-null counterpart. For these effects, HBx interrupted the action of NRE binding protein via methylation of the C-1619 within NRE, resulting in activation of the core promoter. Treatment with 5-Aza-2′dC or DNMT1 knock-down drastically impaired the ability of HBx to activate the core promoter and stimulate HBV replication in 1.2-mer HBV replicon and in vitro infection systems, indicating the positive role of HBx-mediated cccDNA methylation in HBV replication.

• Journal of the Korean Wood Science and Technology
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• 제17권2호
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• pp.34-64
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• 1989

포장(包裝) 용적(容積) 감소에 따른 수송비(輸送費) 절감(節減) 효과(效果)가 있어 조립시(組立式) 탁자류(卓子類) 가구(家具)의 제작(製作)에 널리 쓰이는 CBA(corner block with anchor bolt) 접합방식(接合方式)은 일정기간(一定期間) 사용(使用)함에 따라 접합부위(接合部位)가 약해지고 그 결과(結果) 구조(構造)가 불안정(不安定)하게 되는 반강접합(半剛接合)(semi-rigid joint) 특유(特有)의 결점(缺點)도 지니고 있다. 따라서 본(本) 연구(硏究)에서는 CBA 접합(接合) 강도(强度)에 영향하는 주요(主要) 설계(設計) 인자(因子)로서 side rail 규격, corner block의 side rail에의 부착시(時) 보강재(補强材)의 효과(效果) 및 corner block관통 anchor bolt의 사용(使用) 수(數) 그리고 corner block의 형태등(等)의 평가(評價)를 하기 위해 22개(個)의 접합군(接合群) 별(別)로 총(總) 88개(個)의 table section 시험체(試驗體)를 제작(製作)한 후(後)그들의 강성(剛性) 계수(係數)(Z - 값) 및 유효강도(有效强度)를 수평 하중(荷重)에 의한 변형측정(變形測定) 실험(實驗)을 통해 결정(決定)한 후 설계(設計) 인자별(因子別) 효과(效果)를 비교 분석(分析)하였다. 분석결과(分析結果), side rail의 높이 증대(增大) 및 corner block 부착시(時) PVAc 수지(樹脂)의 사용효과(使用效果)가 뚜렷하여 유효강도(有效强度)의 유의적(有意的) 향상(向上)을 나타냈고 anchor bolt의 효과(效果) 역시 2개 사용시(使用時)가 1개 사용시(使用時) 보다 훨씬 큰 것으로 나타났다. 또 side rail 높이 와 anchor bolt 사용(使用) 수(數)간에는 상호작용(相互作用) 효과(效果)도 있었다. 그러나 side rail의 두께 효과(效果)는 22mm에서 25mm로 증대(增大)시켰을때 뚜렷한 상승 경향(傾向)은 보여주지 못했다. 한편 corner block의 형태는 MDF를 주재료(主材料)로 사용(使用)한 탁자(卓子) 설계시(設計時)는 두께 25mm, 높이 100mm의 side rail에 PVAc 수지(樹脂)로 보강(補强)하고 mitered corner block에 2개(個)의 anchor bolt를 관통시킨 경우가 유효강도(有效强度) 3171.7 kgf-cm로 22개의 접태군(接台群)들 중 최대치(最大値)를 나타냄으로써 miter type이 rectangular type보다 바람직한 것으로 나타났다. 결론적(結論的)으로 자재(資材)의 효과적(效果的) 이용(利用)을 통한 생산비(生産費) 절감(節減)과 동시(同時)에 구조(構造)의 안정(安定)된 강도적(强度的) 측면(側面)을 고려할 때, 두께 22mm, 높이 75mm의 MDF side rail에 mitered corner block을 PVAc 수지(樹脂)와 나사못을 이용하여 부착한 후(後) 2개(個)의 anchor bolt를 관통시키는 방법(方法)을 가장 합리적(合理的)인 MDF 사용(使用) 조립시(組立式) 탁자(卓子) 설계(設計) 방안(方案)으로 제시(提示)하는 바이다.

• Molecules and Cells
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• 제38권2호
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• pp.130-137
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• 2015

MicroRNAs (miRNAs) are small, endogenous RNAs that play important gene-regulatory roles by binding to the imperfectly complementary sequences at the 3'-UTR of mRNAs and directing their gene expression. Here, we first discovered that miR-576-3p was down-regulated in human bladder cancer cell lines compared with the non-malignant cell line. To better characterize the role of miR-576-3p in bladder cancer cells, we over-expressed or down-regulated miR-576-3p in bladder cancer cells by transfecting with chemically synthesized mimic or inhibitor. The overexpression of miR-576-3p remarkably inhibited cell proliferation via G1-phase arrest, and decreased both mRNA and protein levels of cyclin D1 which played a key role in G1/S phase transition. The knock-down of miR-576-3p significantly promoted the proliferation of bladder cancer cells by accelerating the progression of cell cycle and increased the expression of cyclin D1. Moreover, the dual-luciferase reporter assays indicated that miR-576-3p could directly target cyclin D1 through binding its 3'-UTR. All the results demonstrated that miR-576-3p might be a novel suppressor of bladder cancer cell proliferation through targeting cyclin D1.

• 생명과학회지
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• 제26권7호
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• pp.826-834
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• 2016

본 연구는 Hsp90 inhibitor 및 SIRT1 inhibitor의 병용처리가 항암제 다제내성(MDR) 인간 암세포의 증식 억제에 효과적임을 밝혔다. SIRT1 활성 억제가 Hsp90 inhibitor인 17-AAG의 세포 독성의 효과를 증강시켰으며, 이로 인해 Hsp90 inhibitors에 대한 내성을 극복시킬 수 있음을 인간 자궁암세포인 HeyA8의 MDR 변이주인 HeyA8- MDR 세포에서 확인하였다. SIRT1 inhibitor는 Hsp90 inhibitor에 의한 Hsp90 샤페론 기능 억제를 증강시키며, ubiquitin ligase CHIP의 발현 증강을 유발하여, Hsp90 client protein 인 mutant p53 (mut p53)의 분해를 촉진시킨다. Mut p53 의 발현 감소는 암세포의 Hsp90 inhibitor 내성 획득의 가장 중요한 원인으로 지적되는 heat shock factor 1 (HSF1)/heat shock proteins (Hsps)의 발현 억제와 관련됨을 알 수 있었으며, 이는 항암제 다제내성 세포에서 SIRT1 inhibitor에 의하여 Hsp90 inhibitor에 대한 감수성이 증강되는 분자적 기전임을 밝혔다. 그러므로, SIRT1 억제에 의한 mut p53/HSF1 발현 감소가 MDR 암세포의 Hsp90 inhibitors 내성 극복에 매우 유효함을 시사하는 결과를 얻었다.

• BMB Reports
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• 제48권6호
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• pp.330-335
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• 2015

Apoptosis inhibitor 5 (API5) has recently been identified as a tumor metastasis-regulating gene in cervical cancer cells.However, the precise mechanism of action for API5 is poorly understood. Here, we show that API5 increases the metastatic capacity of cervical cancer cells in vitro and in vivo via up-regulation of MMP-9. Interestingly, API5-mediated metastasis was strongly dependent on the Erk signaling pathway. Conversely, knock-down of API5 via siRNA technology decreased the level of phospho-Erk, the activity of the MMPs, in vitro invasion, and in vivo pulmonary metastasis. Moreover, the Erk-mediated metastatic action was abolished by the mutation of leucine into arginine within the heptad leucine repeat region, which affects protein-protein interactions. Thus, API5 increases the metastatic capacity of tumor cells by up-regulating MMP levels via activation of the Erk signaling pathway. [BMB Reports 2015; 48(6): 330-335]

• 한국미생물·생명공학회지
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• 제44권2호
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• pp.194-200
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• 2016

Resveratrol은 포도, 오디, 땅콩과 같은 많은 과일과 채소에 존재하는 폴리페놀 화합물로써 다양한 생물학적 효과를 가진다고 보고되어있다. 그러나, resveratrol이 A549 폐암세포에서 유도하는 apoptosis에 관여하는 분자적 기전 및 anoikis에 관해서는 명백하게 밝혀지지 않았다. 본 연구에서, 우리는 정상적인 p53 유전자를 갖는 A549 세포에서 resveratrol의 효과를 조사하고, p53 유전자가 결실된 SKOV3 난소암 세포와 그 효과를 비교했다. Resveratrol은 확실하게 SKOV3 세포에 비해 농도, 시간의존적으로 A549 세포의 생존과 증식을 억제했다. 또한 resveratrol은 A549 세포의 apoptosis를 유도했지만 세포의 anoikis 저항성에는 영향을 미치지 않았다. 더불어, p53 유전자 기능이 불완전 소실된(knock-down) A549 세포의 생존과 증식은 resveratrol에 의해 변하지 않았다. 그러므로, 본 연구의 결과는 resveratrol의 항암 효과가 기능을 하는 p53 유전자의 존재에 의존한다는 것을 보여준다. 결론적으로, 우리는 resveratrol이 p53 유전자에 의존적으로 A549 세포에 대해 항암효과를 가진다는 것을 입증했다.

• 동의생리병리학회지
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• 제25권5호
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• pp.843-848
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• 2011

In Korea, China, and Japan, Paeonia lactiflora Pall (PL) has been used in the treatment of rheumatoid arthritis, hepatitis, and fever for more than 1200 years. It has been reported that PL has protective effects against $H_2O_2$-induced oxidative stress and LPS-induced liver inflammation. However cellular and molecular mechanism of PL protection against oxidative stress has not fully been elucidated. Here, we describe that the water-soluble extract of PL decreased $H_2O_2$-induced hepatotoxicity. This hepatoprotective effect of PL is reason to decrease the level of intracellular reactive oxygen species (ROS) and increase expression of heme oxygenase 1 (HO-1) and heat shock protein 72 (HSP72) which proteins are involved in protecting the cells from stress like as oxidative stress. We also elucidated that hepatoprotective effect of PL was abolished by knock down of HO-1 and HSP72 by siRNA. These results suggest that the increasing of HO-1 and HSP72 protein by PL treatment might be participated in hepatoprotective effect against oxidative stress such as $H_2O_2$.

• The Korean Journal of Physiology and Pharmacology
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• 제14권1호
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• pp.15-20
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• 2010

It has been shown that CA repeats in the 3'-untranslated region (UTR) of bcl-2 mRNA contribute the constitutive decay of bcl-2 mRNA and that hnRNP L (heterogenous nuclear ribonucleoprotein L) interacts with CA repeats in the 3'-UTR of bcl-2 mRNA, both in vitro and in vivo. The aim of this study was to determine whether the alteration of hnRNP L affects the stability of bcl-2 mRNA in vivo. Human breast carcinoma MCF-7 cells were transfected with hnRNP L-specific shRNA or hnRNP L-expressing vector to decrease or increase hnRNP L levels, respectively, followed by an actinomycin D chase. An RT-PCR analysis showed that the rate of degradation of endogenous bcl-2 mRNA was not affected by the decrease or increase in the hnRNP L levels. Furthermore, during apoptosis or autophagy, in which bcl-2 expression has been reported to decrease, no difference in the degradation of bcl-2 mRNA was observed between control and hnRNP L-knock down MCF-7 Cells. On the other hand, the levels of AUF-1 and nucleolin, transacting factors for ARE in the 3'UTR of bcl-2 mRNA, were not significantly affected by the decrease in hnRNP L, suggesting that a disturbance in the quantitative balance between these transacting factors is not likely to interfere with the effect of hnRNP L. Collectively, the findings indicate that the decay of bcl-2 mRNA does not appear to be directly controlled by hnRNP L in vivo.