• BMB Reports
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• 제39권2호
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• pp.132-139
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• 2006

Vascular endothelial cadherin (VE-cadherin), which belongs to the classical cadherin family, is localized at adherens junctions exclusively in vascular endothelial cells. Biochemical and biomechanical cues regulate the VE-cadherin adhesive potential by triggering the intracellular signals. VE-cadherin-mediated cell adhesion is required for cell survival and endothelial cell deadhesion is required for vascular development. It is therefore crucial to understand how VE-cadherin-based cell adhesion is controlled. This review summarizes the inter-endothelial cell adhesions and introduces our recent advance in Rap1-regulated VE-cadherin adhesion. A further analysis of the VE-cadherin recycling system will aid the understanding of cell adhesion/deadhesion mechanisms mediated by VE-cadherin in response to extracellular stimuli during development and angiogenesis.

• BMB Reports
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• 제47권10호
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• pp.552-557
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• 2014

The main purpose of this study was to investigate whether type 3 muscarinic acetylcholine receptor (M3R) dysfunction induced vascular hyperpermeability. Transwell system analysis showed that M3R inhibition by selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and small interfering RNA both increased endothelial permeability. Using coimmunoprecipitation and Western blot assay, we found that M3R inhibition increased VE-cadherin and ${\beta}$-catenin tyrosine phosphorylation without affecting their expression. Using PTP1B siRNA, we found that PTP1B was required for maintaining VE-cadherin and ${\beta}$-catenin protein dephosphorylation. In addition, 4-DAMP suppressed PTP1B activity by reducing cyclic adenosine monophosphate (cAMP), but not protein kinase $C{\alpha}$ ($PKC{\alpha}$). These data indicate that M3R preserves the endothelial barrier function through a mechanism potentially maintaining PTP1B activity, keeping the adherens junction proteins (AJPs) dephosphorylation.

• BMB Reports
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• 제48권8호
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• pp.429-430
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• 2015

Angiogenesis is a complex process involving dynamic interaction of various cell to cell interactions. Endothelial cell interactions regulated by growth factors, inflammatory cytokines, or hemodynamic stress are critical for balancing vascular quiescence and activation. Yes-associated protein (YAP), an effector of Hippo signaling, is known to play significant roles in maintaining cellular homeostasis. However, its role in endothelial cells for angiogenic regulation remains relatively unexplored. We demonstrated the critical role of YAP in vascular endothelial cells and elucidated the underlying molecular mechanisms involved in angiogenic regulation of YAP. YAP was expressed in active angiogenic regions where endothelial cell junctions were relatively loosened. Consistently, YAP subcellular localization and activity were regulated by VE-cadherin-mediated PI3K/Akt pathway. YAP thereby regulated endothelial sprouting via angiopoietin-2 expression. These results provide an insight into a model of coordinating endothelial junctional stability and angiogenic activation through YAP. [BMB Reports 2015; 48(8): 429-430]

• Environmental Analysis Health and Toxicology
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• 제22권2호통권57호
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• pp.137-145
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• 2007

The effect of cadmium chloride $(CdCl_2)$ on the expression of E-cadherin was examined in bEnd.3 mouse brain endothelial cells. $CdCl_2$ induced $PGE_2$ release, which were blocked by non-steroidal antinflamatory drugs (NSAIDs) such as indomethacin and NS398 indicating the expression of COX-2 might contribute to $PGE_2$ production. $CdCl_2$ decreased the expression of E-cadherin, but not VE-cadherin at levels of mRNA and protein. Reduced expression level of E-cadherin was restored by NSAIDs, which was reversed by the addition of $PGE_2$. $CdC_2$-induced decrease of E-cadherin level was also recovered by antioxidants including N-acetylcyteine (NAC) and trolox. Together with previous report which showed $CdCl_2$ induced COX-2 expression in a cellular oxidative stress dependent manner, these data suggest that $CdCl_2$ decreases E-cadherin expression through induction of cellular oxidative stress and in turn COX-2 expression in brain endothelial cells.

• KSBB Journal
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• 제24권2호
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• pp.122-130
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• 2009

선별한 신생혈관형성억제제는 EGCG보다도 제어 효과가 나은 천연산물들 중에서 전호, 파고지, 희첨 및 중심으로 그 기전을 밝히고자 하였다. 세포독성은 전호는 0.3 ppm에서 약간의 독성을 나타내었고, 파고지는 10 ppm까지는 독성을 나타내지 않았으며, 희첨 및 산수유는 25 ppm까지 독성을 나타내지 않았다. 세포부착억제작용은 신생혈관의 형성에 중요한 역할을 하기 때문에 cell adhesion 분자인 VCAM-1, ICAM-1 및 E-selectin들에 대하여 ELISA 법으로 살펴보았다. VCAM-1에 대한 천연산물의 작용은 전호 (0.2 ppm, 125%)>파고지 (0.5 ppm, 100%)>희첨 (5.0 ppm, 114%)> 산수유 (5.0 ppm, 111.8%)의 순으로 저해의 강도가 높으며, ICAM-1은 전호 (0.25 ppm, 130%)>파고지 (0.5 ppm, 100%)>희첨 (5.0 ppm, 138%)>산수유 (5.0 ppm, 66.7%)의 순으로 저해되는 것으로 나타났고, 그리고 E-Selectin은 전호 (0.25 ppm, 100%)> 파고지 (1.0 ppm, 128%)>희첨 (5.0 ppm, 120%)>산수유 (5.0 ppm, 100.7%)의 순으로 저해되는 것으로 나타났다. Western blot으로부터, 전호 추출물은 VE-cadherin과 ${\beta}$-catenin의 신호전달을 억제하였으며, 그 하위 신호 전달분자인 Akt도 억제하는 것으로 나타났고, 파고지는 ${\beta}$-catenin의 신호는 억제하지 않는 것으로 보이나, 그 하위그룹의 Akt의 신호전달을 억제하는 것으로 나타났다. 그리고, 희첨은 VE-Cadherin과 하위 그룹의 Akt를 농도의 증가에 따라 확실한 제어를 보이고 있음을 알 수 있었고, 산수유는 하위그룹의 Akt의 신호전달을 억제하는 것으로 나타났다. 4종류의 선택된 천연산물은 세포표면의 신호전달분자 그리고 그 하위 그룹의 Akt를 억제함으로써 NF-kB의 활성을 차단함으로써 신생혈관의 형성을 억제하는 것으로 판단된다. 따라서 4종류의 천연산물 전호, 파고지, 희첨 및 산수유는 전반적으로 낮은 농도에서 세포부착인자의 발현을 억제하였고, 신호전달 분자들을 억제함으로써 신생혈관 형성 억제에 따른 항비만제제로서 충분한 가능성을 보였다.

• Biomolecules & Therapeutics
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• 제24권2호
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• pp.132-139
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• 2016

The endothelial-mesenchymal transition (EndMT) is known to be involved in the transformation of vascular endothelial cells to mesenchymal cells. EndMT has been confirmed that occur in various pathologic conditions. Transforming growth factor ${\beta}1$ (TGF-${\beta}1$) is a potent stimulator of the vascular endothelial to mesenchymal transition (EMT). Aspirin-triggered resolvin D1 (AT-RvD1) has been known to be involved in the resolution of inflammation, but whether it has effects on TGF-${\beta}1$-induced EndMT is not yet clear. Therefore, we investigated the effects of AT-RvD1 on the EndMT of human umbilical vein vascular endothelial cells line (HUVECs). Treatment with TGF-${\beta}1$ reduced the expression of Nrf2 and enhanced the level of F-actin, which is associated with paracellular permeability. The expression of endothelial marker VE-cadherin in HUVEC cells was reduced, and the expression of mesenchymal marker vimentin was enhanced. AT-RvD1 restored the expression of Nrf2 and vimentin and enhanced the expression of VE-cadherin. AT-RvD1 did also affect the migration of HUVEC cells. Inhibitory ${\kappa}B$ kinase 16 (IKK 16), which is known to inhibit the NF-${\kappa}B$ pathway, had an ability to increase the expression of Nrf2 and was associated with the inhibition effect of AT-RvD1 on TGF-${\beta}1$-induced EndMT, but it had no effect on TGF-${\beta}1$-induced EndMT alone. Smad7, which is a key regulator of TGF-${\beta}$/Smads signaling by negative feedback loops, was significantly increased with the treatment of AT-RvD1. These results suggest the possibility that AT-RvD1 suppresses the TGF-${\beta}1$-induced EndMT through increasing the expression of Smad7 and is closely related to oxidative stress.

• 한국가시화정보학회지
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• 제15권3호
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• pp.41-46
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• 2017

The apoptosis of macrophages occurs throughout all stages of atherosclerosis. It is known to constitute atheromatous plaque, increase plaque instability, and thus contribute to the development of atherosclerosis. However, there still remains much to be elucidated on how the apoptotic macrophages affect the endothelial cells and also how they contribute to the development of atherosclerosis. Here we present a microfluidic system, which enables co-culture of apoptotic macrophages and endothelial cells in fibrin gel that mimics in vivo extracellular matrix. With the system, we can investigate the effect of macrophage apoptosis on vascular endothelial cells by quantitatively analyzing the level of reactive oxygen species of HUVECs, integrity of VE-cadherin and cell proliferation. We expect that this system could be utilized further for understanding different mechanisms of apoptotic macrophage on the development of atherosclerosis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8225-8228
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• 2014

Glioma is one of the most common tumors in China and chemotherapy is critical for its treatment. Recent studies showed that benzyl isothiocyanate (BITC) could inhibit the growth of glioma cells, but the mechanisms are not fully understood. This study explored the inhibitory effect of BITC on invasion and angiogenesis of U87MG human glioma cells in vitro and in vivo, as well as potential mechanisms. It was found that BITC could inhibit invasion and angiogenesis of human glioma U87MG cells by inducing cell cycle arrest at phase G2/M. It also was demonstrated that BITC decreased expression of cyclin B1, p21, MMP-2/9, VE-cadherin, CD44, CXCR4 and MTH1, the activity of the telomerase and $PKC{\zeta}$ pathway. Microarray analysis was thus useful to explore the potential target genes related to tumorigenic processes. BITC may play important roles in the inhibition of invasion and angiogenesis of human glioma cells.

• 한국해양바이오학회지
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• 제1권3호
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• pp.156-162
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• 2006

The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/mL$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited non-activated U937 monocytic cell adhesion to HUVECs activated with IL-$1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with IL-$1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to IL-$1{\beta}$ stimulated HUVECs was completely suppressed by 121% at a concentration of 18.5 ug/mL. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin and VE-cadherin to NF-kB based on western bolt analysis. And also inhibited IL-1-stimulated HUVEC expression of the adhesion molecules, ICAM-1 by 40%, VCAM-1 by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities and non-toxicity may be expected from these results.

• Journal of Microbiology and Biotechnology
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• 제16권10호
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• pp.1544-1553
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• 2006

The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/ml$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited cell adhesion that non-activated U937 monocytic cell adhesion to HUVECs activated with $IL-1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with $IL-1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to $IL-1{\beta}$-stimulated HUVECs was completely suppressed by 121% at a concentration of $18.5{\mu}g/ml$. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin, and VE-cadherin to NF-kB, based on western bolt analysis. It also inhibited IL-l-stimulated HUVEC expression of the adhesion molecules, ICAM-l by 40%, VCAM-l by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities, and non-toxicity may be expected from these results.