• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.171-176
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• 2008

Heat shock proteins (HSPs) serve as molecular chaperones and play a role in cell protection from damage in response to stress stimuli. The aim of this article is to investigate whether HSP22 affects IL-8 expression in vascular smooth muscle cells (VSMCs), and which cellular factors are involved in the HSP-mediated IL-8 induction in that cell type in terms of mitogen activated protein kinase (MAPK) and transcription element. Exposure of aortic smooth muscle cells (AoSMCs) to HSP22 not only enhanced IL-8 release but also induced IL-8 transcript via promoter activation. HSP22 activated ERK and p38 MAPK in AoSMCs. HSP22-induced IL-8 release was inhibited by U0126, but not by SB202190. A mutation in the IL-8 promoter region at the binding site of NF-${\kappa}$ B, but not AP-1 or C/EBP, impaired promoter activation in response to HSP22. Delivery of I ${\kappa}$ B, but not dominant negative c-Jun, lowered HSP22-induced IL-8 release from AoSMCs. These results suggest that HS P22 induces IL-8 in VSMCs via ERK1/2, and that transcription factor NF-kB may be required for the HSP22-induced IL-8 up-regulation.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.137-142
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• 2008

Ceramide has emerged as a novel second messenger for intracellular signalling. It is produced from sphingomyelin and is involved in the control of cell differntiation, proliferation, and apoptosis. $C_2$-ceramide, short chain ceramide, plays a role in mediating contraction of cat esophageal smooth muscle cells. We examined the effect of synthesized ceramide analogues on the $C_2$-ceramide and ACh-induced contraction in esophageal smooth muscle cells isolated with collagenase. CY3523, CY3525, or CY3723 inhibited $C_2$-ceramide induced contraction, in a time dependent manne. Each analogue also inhibited the contraction in concentration dependent manners. CY 3523, CY 3525, and CY 3723 had no effect to the contraction induced by PMA. The inhibition with CY3523, CY3525 and CY3723 on the $C_2$-ceramide induced contraction was recovered by PMA. These analogues decreased the density of MAPK bands (p44/42 or p38) in the western blot. These results suggest that ceramide analogues can inhibit $C_2$-ceramide induced contraction via PKC and MAPK dependent pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.2
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• pp.73-77
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• 2008

Recent studies have documented that testosterone relaxes several smooth muscles by modulating $K^+$ channel activities. Smooth muscles of seminal vesicles playa fundamental role in ejaculation, which might involve testosterone. This study was aimed to assess the role of testosterone in seminal vesicular motility by studying its effects on contractile agents and on the ion channels of single vesicular myocytes in a rabbit model. The contractile responses of circular smooth muscle strips of rabbit seminal vesicles to norepinephrine ($10{\mu}M$), a high concentration of KCI (70 mM), and testosterone ($10{\mu}M$) were observed. Single vesicular myocytes of rabbit were isolated using proteolytic enzymes including collagenase and papain. Inside-out, attached, and whole-cell configurations were examined using the patch clamp technique. The applications of $10{\mu}M$ norepinephrine or 70 mM KCl induced tonic contractions, and $10{\mu}M$ testosterone (pharmacological concentration) evoked dose-dependent relaxations of these precontracted strips. Various $K^+$ channel blockers, such as tetraethylammonium (TEA; $10{\mu}M$), iberiotoxin ($0.1{\mu}M$), 4-aminopyridine (4-AP, $10{\mu}M$), or glibenclamide ($10{\mu}M$) rarely affected these relaxations. Single channel data (of inside-out and attached configurations) of BK channel activity were also hardly affected by testosterone ($10{\mu}M$). On the other hand, however, testosterone reduced L-type $Ca^{2+}$ currents significantly, and found to induce acute relaxation of seminal vesicular smooth muscle and this was mediated, at least in part, by $Ca^{2+}$ current inhibition in rabbit.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.139-147
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• 2013

Lysolipids such as LPA, S1P and SPC have diverse biological activities including cell proliferation, differentiation, and migration. We investigated signaling pathways of LPA-induced contraction in feline esophageal smooth muscle cells. We used freshly isolated smooth muscle cells and permeabilized cells from cat esophagus to measure the length of cells. Maximal contraction occurred at $10^{-6}M$ and the response peaked at 30s. To identify LPA receptor subtypes in cells, western blot analysis was performed with antibodies to LPA receptor subtypes. LPA1 and LPA3 receptor were detected at 50 kDa and 44 kDa. LPA-induced contraction was almost completely blocked by LPA receptor (1/3) antagonist KI16425. Pertussis toxin (PTX) inhibited the contraction induced by LPA, suggesting that the contraction is mediated by a PTX-sensitive G protein. Phospholipase C (PLC) inhibitors U73122 and neomycin, and protein kinase C (PKC) inhibitor GF109203X also reduced the contraction. The PKC-mediated contraction may be isozyme-specific since only $PKC{\varepsilon}$ antibody inhibited the contraction. MEK inhibitor PD98059 and JNK inhibitor SP600125 blocked the contraction. However, there is no synergistic effect of PKC and MAPK on the LPA-induced contraction. In addition, RhoA inhibitor C3 exoenzyme and ROCK inhibitor Y27632 significantly, but not completely, reduced the contraction. The present study demonstrated that LPA-induced contraction seems to be mediated by LPA receptors (1/3), coupled to PTX-sensitive G protein, resulting in activation of PLC, PKC-${\varepsilon}$ pathway, which subsequently mediates activation of ERK and JNK. The data also suggest that RhoA/ROCK are involved in the LPA-induced contraction.

• Journal of the Korean Institute of Landscape Architecture
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• v.30 no.2
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• pp.50-62
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• 2002

From modernism to post-modernism, the practice in the design field often reduced the complexity of environment and to remove variety. However, contemporary ideas of space have been changed. The current thought premise is that the environment is mutable and is evolving according to inner and outer forces and elements. Therefore, leading designers recognize that the environment is complex in itself while anticipating a new theory explaining on-going trends. The idea of fold formulated by Gilles Deleuze can provide a theoretical base for new environmental design in constrat to current design practices. The fold is a hybrid by accommodating complex relations within an object. It carries a dynamic world view through continual process and yields a topological space against absolute space like Euclid geometry. The characteristics of the fold can be paraphrased as rhizome, stratification and smooth space. Rhizome forms a non-hierarchial connection like networking in internet space. Stratification is a kind of superimposition of autonomous potential layers within a single object. Smooth space is a free space and event oriented space keeping non-linear form. This study tried to incorporate the idea of fold to environmental design methods and design process in order to make space which can correspond with complex environment and topological form. In the design process adapted to fold theory, rhizome analysis accepts the complexity of environment and stratification strategy embraces the possibility of accidental use. As a result, the designed park carries a monadic image and produces an ambiguous space. Lastly, smooth space makes topological space unlike Euclid geometry and is free space comosed by the user themselves. Transporting the idea of fold into environmental design could be an alterative way for indeterminate and flexible design to accept new identity of place. Therefore, this study accepts the concept of incidental morphogenesis to make space based on the complexity of environment. The designed space based on the idea of fold searches to create free event space determined by user rather than designated by designer.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.549-555
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• 2015

We attempted to investigate molecular mechanisms underlying phenotypic change of vascular smooth muscle cells (VSMCs) by determining signaling molecules involved in chemokine production. Treatment of human aortic smooth muscle cells (HAoSMCs) with thrombin resulted not only in elevated transcription of the (C-C motif) ligand 11 (CCL11) gene but also in enhanced secretion of CCL11 protein. Co-treatment of HAoSMCs with GF109230X, an inhibitor of protein kinase C, or GW5074, an inhibitor of Raf-1 kinase, caused inhibition of ERK1/2 phosphorylation and significantly attenuated expression of CCL11 at transcriptional and protein levels induced by thrombin. Both Akt phosphorylation and CCL11 expression induced by thrombin were attenuated in the presence of pertussis toxin (PTX), an inhibitor of Gi protein-coupled receptor, or LY294002, a PI3K inhibitor. In addition, thrombin-induced production of CCL11 was significantly attenuated by pharmacological inhibition of Akt or MEK which phosphorylates ERK1/2. These results indicate that thrombin is likely to promote expression of CCL11 via PKC/Raf-1/ERK1/2 and PTX-sensitive protease-activated receptors /PI3K/Akt pathways in HAoSMCs. We propose that multiple signaling pathways are involved in change of VSMCs to a secretory phenotype.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.397-403
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• 2011

The proliferation, migration, cytokine release, and contraction of airway smooth muscle cells are key events in the airway remodeling process that occur in lung disease such as asthma, chronic obstruction pulmonary disease, and cancer. These events can be modulated by a number of factors, including cigarette smoke extract (CSE). CSE-induced alterations in the viability, migration, and contractile abilities of normal human airway cells remain unclear. This study investigated the effect of CSE on cell viability, migration, tumor necrosis factor (TNF)-${\alpha}$ secretion, and contraction in normal human bronchial smooth muscle cells (HBSMCs). Treatment of HBSMCs with 10% CSE induced cell death, and the death was accompanied by the generation of reactive oxygen species (ROS). CSE-induced cell death was reduced by N-acetyl-l-cysteine (NAC), an ROS scavenger. In addition, CSE reduced the migration ability of HBSMCs by 75%. The combination of NAC with CSE blocked the CSE-induced reduction of cell migration. However, CSE had no effect on TNF-${\alpha}$ secretion and NF-${\kappa}B$ activation. CSE induced an increase in intracellular $Ca^{2+}$ concentration in 64% of HBSMCs. CSE reduced the contractile ability of HBSMCs, and the ability was enhanced by NAC treatment. These results demonstrate that CSE treatment induces cell death and reduces migration and contraction by increasing ROS generation in normal HBSMCs. These results suggest that CSE may induce airway change through cell death and reduction in migration and contraction of normal HBSMCs.

• Journal of the Earthquake Engineering Society of Korea
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• v.17 no.1
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• pp.1-10
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• 2013

In order to predict inelastic displacement response without nonlinear dynamic analysis, the equal displacement rule can be used for the structures with longer natural periods than the characteristic period, $T_g$, of earthquake record. In the period range longer than $T_g$, peak displacement responses of elastic systems are equal or larger than those of inelastic systems. In the period range shorter than $T_g$, opposite trend occurs. In the equal displacement rule, it is assumed that peak displacement of inelastic system with longer natural period than $T_g$ equals to that of elastic system with same natural period. The equal displacement rule is very useful for seismic design purpose of structures with longer natural period than $T_g$. In the period range shorter than $T_g$, the peak displacement of inelastic system can be simply evaluated from the peak displacement of elastic system by using the inelastic displacement ratio, which is defined as the ratio of the peak inelastic displacement to the peak elastic displacement. Smooth hysteretic behavior is more similar to actual response of real structural system than a piece-wise linear hysteretic behavior such as bilinear or stiffness degrading behaviors. In this paper, the inelastic displacement ratios of the smooth hysteretic behavior system are evaluated for far-fault and near-fault earthquakes. The simple formula of inelastic displacement ratio considering the effect of $T_g$ is proposed.

• Transactions of the Korean Society of Mechanical Engineers B
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• v.21 no.9
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• pp.1207-1217
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• 1997

The present work experimentally investigated the effects of mass flux, heat flux, inlet quality on the heat transfer performance inside the U-bend of smooth and microfin tube using R-22 and R-407C refrigerants. The parameters were 200 and 400 kg/m$^{2}$ s for mass flux, 6 and 12 kw/m$^{2}$ for heat flux, 0.1 and 0.2 for inlet quality under the pressure of 0.65 MPa. The apparatus consisted of the test section of four straight sections and three U-bends, preheater, condenser, refrigerant pump, mass flow meter etc. The average heat transfer coefficient at the downstream straight section after U-bend was affected by U-bend due to the centrifugal force and mixing of two-phase flow in the U-bend. The average heat transfer coefficient at the U-bend was 4 ~ 33 % higher than that at the straight section. The average heat transfer coefficients were affected in the order of mass flux, heat flux and inlet quality. The average heat transfer coefficients in the microfin tube were lager by 19 ~ 49% and 33 ~ 69% than that in the smooth tube at the straight section and at the U-bend separately. The average heat transfer coefficients for R-407C were larger by 33 ~ 41% and 17 ~ 29% than that for R-22 in the smooth tube and the microfin tube separately.

• Molecules and Cells
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• v.41 no.3
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• pp.198-206
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• 2018

Aortic dissection (AD) is a catastrophic disease with high mortality and morbidity, characterized with fragmentation of elastin and loss of smooth muscle cells. Although AD has been largely attributable to polymorphisms defect in the elastin-coding gene, tropoelastin (TE), other undermined factors also appear to play roles in AD onset. Here, we investigated the effects of post-transcriptional control of TE by microRNAs (miRNAs) on elastin levels in aortic smooth muscle cells (ASMC). We found that miR-144-3p is a miRNA that targets TE mRNA in both human and mouse. Bioinformatics analyses and dual luciferase reporter assay showed that miR-144-3p inhibited protein translation of TE, through binding to the 3'-UTR of the TE mRNA. Interestingly, higher miR-144-3p levels and lower TE were detected in the ASMC obtained from AD patients, compared to those from non-AD controls. In a mouse model for human AD, infusion of adeno-associated viruses (serotype 6) carrying antisense for miR-144-3p (asmiR-144-3p) under CAG promoter significantly reduced the incidence and severity of AD, seemingly through enhancement of TE levels in ASMC. Thus, our data suggest an essential role of miR-144-3p on the pathogenesis of AD.