• Title/Summary/Keyword: Egr1

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Lysophosphatidic acid increases mesangial cell proliferation in models of diabetic nephropathy via Rac1/MAPK/KLF5 signaling

  • Kim, Donghee;Li, Hui Ying;Lee, Jong Han;Oh, Yoon Sin;Jun, Hee-Sook
    • Experimental and Molecular Medicine
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    • v.51 no.2
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    • pp.9.1-9.10
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    • 2019
  • Mesangial cell proliferation has been identified as a major factor contributing to glomerulosclerosis, which is a typical symptom of diabetic nephropathy (DN). Lysophosphatidic acid (LPA) levels are increased in the glomerulus of the kidney in diabetic mice. LPA is a critical regulator that induces mesangial cell proliferation; however, its effect and molecular mechanisms remain unknown. The proportion of ${\alpha}-SMA^+/PCNA^+$ cells was increased in the kidney cortex of db/db mice compared with control mice. Treatment with LPA concomitantly increased the proliferation of mouse mesangial cells (SV40 MES13) and the expression of cyclin D1 and CDK4. On the other hand, the expression of $p27^{Kip1}$ was decreased. The expression of $Kr{\ddot{u}}ppel$-like factor 5 (KLF5) was upregulated in the kidney cortex of db/db mice and LPA-treated SV40 MES13 cells. RNAi-mediated silencing of KLF5 reversed these effects and inhibited the proliferation of LPA-treated cells. Mitogen-activated protein kinases (MAPKs) were activated, and the expression of early growth response 1 (Egr1) was subsequently increased in LPA-treated SV40 MES13 cells and the kidney cortex of db/db mice. Moreover, LPA significantly increased the activity of the Ras-related C3 botulinum toxin substrate (Rac1) GTPase in SV40 MES13 cells, and the dominant-negative form of Rac1 partially inhibited the phosphorylation of p38 and upregulation of Egr1 and KLF5 induced by LPA. LPA-induced hyperproliferation was attenuated by the inhibition of Rac1 activity. Based on these results, the Rac1/MAPK/KLF5 signaling pathway was one of the mechanisms by which LPA induced mesangial cell proliferation in DN models.

High Glucose Induces Connective Tissue Growth Factor Expression and Extracellular Matrix Accumulation in Rat Aorta Vascular Smooth Muscle Cells Via Extracellular Signal-Regulated Kinase 1/2

  • Ha, Yu Mi;Lee, Dong Hyup;Kim, Mina;Kang, Young Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.4
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    • pp.307-314
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    • 2013
  • Connective tissue growth factor (CTGF) is a potent pro-fibrotic factor, which is implicated in fibrosis through extracellular matrix (ECM) induction in diabetic cardiovascular complications. It is an important downstream mediator in the fibrotic action of transforming growth factor ${\beta}$ ($TGF{\beta}$) and is potentially induced by hyperglycemia in human vascular smooth muscle cells (VSMCs). Therefore, the goal of this study is to identify the signaling pathways of CTGF effects on ECM accumulation and cell proliferation in VSMCs under hyperglycemia. We found that high glucose stimulated the levels of CTGF mRNA and protein and followed by VSMC proliferation and ECM components accumulation such as collagen type 1, collagen type 3 and fibronectin. By depleting endogenous CTGF we showed that CTGF is indispensable for the cell proliferation and ECM components accumulation in high glucose-stimulated VSMCs. In addition, pretreatment with the MEK1/2 specific inhibitors, PD98059 or U0126 potently inhibited the CTGF production and ECM components accumulation in high glucose-stimulated VSMCs. Furthermore, knockdown with ERK1/2 MAPK siRNA resulted in significantly down regulated of CTGF production, ECM components accumulation and cell proliferation in high glucose-stimulated VSMCs. Finally, ERK1/2 signaling regulated Egr-1 protein expression and treatment with recombinant CTGF reversed the Egr-1 expression in high glucose-induced VSMCs. It is conceivable that ERK1/2 MAPK signaling pathway plays an important role in regulating CTGF expression and suggests that blockade of CTGF through ERK1/2 MAPK signaling may be beneficial for therapeutic target of diabetic cardiovascular complication such as atherosclerosis.

The Research for effect of lubricant oil aging on environmental performance (자동차 윤활유의 성상 및 열화가 환경성에 미치는 영향 연구)

  • Kim, Jeong-Hwan;Kim, Ki-Ho;Ha, Jong-Han;Jin, Dong-Young;Myung, Cha-Lee;Jang, Jin-Young
    • Journal of the Korean Applied Science and Technology
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    • v.34 no.1
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    • pp.12-24
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    • 2017
  • The main purpose of this research is for the investigation on the impact of engine oil aging on PM and DPF. It is widely known that lubricant specifications and consumption from an ICE have significantly influenced on the regulated and unregulated harmful emissions as the engine operating conditions. Considering DPF clogging phenomena with lubricant-derived soot/ash components, simulated aging mode for the DPF was newly designed for engine dynamometer testing. PM/ash accumulation cycle were developed in reflecting real-world engine operating conditions for the increment of engine oil consumption and natural DPF regeneration for the ash accumulation. The test duration for DPF aging reached around 100hrs with high- and low-SAPS engine oils, respectively. Using high SAPs engine oil made more PM/ash accumulation compared with low SAPs engine oils and it could accelerate fouling of EGR in engine. Fouling of EGR made effects on more harmful exhaust gases emissions. The test results on engine lubricant under engines operating conditions will deliver for the establishment of regulated and unregulated toxic emissions policy, lubricant quality standard.

Influence of Driving Routes and Seasonal Conditions to Real-driving NOx Emissions from Light Diesel Vehicles (주행 경로 및 계절의 변화가 소형 경유차의 실제 주행 시 질소산화물 배출량에 미치는 영향)

  • Lee, Taewoo;Kim, Jiyoung;Park, Junhong;Jeon, Sangzin;Lee, Jongtae;Kim, Jeongsoo
    • Transactions of the Korean Society of Automotive Engineers
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    • v.22 no.1
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    • pp.148-156
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    • 2014
  • The objective of this study is to compare NOx emissions from light duty diesel vehicles measured from on-road tests that conducted under various driving routes and seasonal conditions. We measured real-driving NOx emissions using PEMS, portable emissions measurement system, under the urban, rural and motorway road traffic conditions. On-road tests were repeated at summer, fall and winter season. The accumulated driving distance is more than 1,200 km per each vehicle. Route average NOx emission factors were compared among nine route-season combinations. The emission characteristics of each combinations were investigated using time series mass emission rates and vehicle operation-based emission rates and activities, which is based on U.S. EPA's MOVES model. Most concerned route-season combination is "urban road condition at summer", which shows two to eleven times higher NOx emissions than other combinations. The emission rates and activities under low speed operating conditions should be managed in order to reduce urban-summer NOx. From a NOx control strategy perspective, the exhaust gas recirculation, EGR, is observed to be properly operated under wide range of vehicle driving conditions in Euro-5 vehicles, even if the air conditioner turns on. In high power demanding conditions, the effect of overspeeding could be more critical than that of air conditioner activation.

Effects of Aromatics and T90 Temperature of Low Cetane Number Fuels on Exhaust Emissions in Low-Temperature Diesel Combustion (저온디젤연소에서 저세탄가 연료의 방향족 및 T90 온도가 배기가스에 미치는 영향)

  • Han, Man-Bae
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.34 no.12
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    • pp.1121-1126
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    • 2010
  • This study is to investigate the effects of aromatics and T90 for low cetane number (CN) fuels on combustion and exhaust emissions in low-temperature diesel combustion. We use a 1.9-L common rail direct injection diesel engine at 1500 rpm and 2.6 bar BMEP. Low temperature diesel combustion was achieved via a high external EGR rate and strategic injection control. The tested fuels four sets: the aromatic content was 20% (A20) or 45% (A45) and the T90 temperature was $270^{\circ}C$ (T270) or $340^{\circ}C$ (T340) with CN 30. Given the engine operating conditions, the T90 was the stronger factor on the ignition delay time, resulting in a longer ignition delay time for higher T90 fuels. All the fuels produced nearly zero PM because of the extension of the ignition delay time induced by the low cetane number. The aromatic content was the main factor that affected the NOx and the NOx increased with the aromatic content.

The Changing Patterns of Demand-Supply and Role of Mineral Resources in Economic Growth during Industrialization of the Republic of Korea (한국공업화과정(韓國工業化過程)에서의 광물자원(鑛物資源)의 수급구조변화(需給構造變化)와 경제성장(經濟成長)에 있어서의 역할(役割))

  • Yun, Suckew
    • Economic and Environmental Geology
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    • v.18 no.1
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    • pp.65-92
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    • 1985
  • A total of 12 mineral commodities significant in domestic output, economy and/or strategy of the Republic of Korea are chosen to examine the structural changes in production and demand-supply of these minerals during the last two decades of her industrialization. These include iron and manganese ores as the raw materials for iron and steel making, copper, zinc and tungsten ores among other non-ferrous metallic minerals, limestone (cement), kaolin, talc, pyrophyllite and graphite among other non-metallic minerals, and anthracite coal as the only domestic source of fossil energy. These are reviewed historically in time-series based on the statistical data which are tabulated and graphed in terms of domestic output, export, import, apparent demand-supply, its increasing rate, and self-sufficiency rate of each commodity. The increasing rates of demand-supply (IRDS) of some more important commodities are compared with those of Gross Domestic Production (GDP) and Economic Growth Rate (EGR) to evaluate how the IRDS contributed to the GDP and EGR. The major results revealed are as follows: Among the 12 commodities, the domestic output of 8 commodities appeared to have grown with steady upward trends: they are ores of lead, zinc and tungsten, limestone (cement), kaolin, talc, pyrophyllite and anthracite coal. Two commodities, ores of iron and copper, continued with unchanging or slightly declining trends and varied fluctuations, in spite of their cardinal importance to the heavy industry and strategy of Korea. The remaining two, graphite and manganese ore, have gradualy declined in domestic output in which the former has still enough resource potential but the latter has not and virtually ceased its domestic output. Trade patterns for mineral commodities in the Republic of Korea during the last two decades have changed greatly, being marked by a shift from mineral-exporting to mineral importing, mainly because of increasing consumption of mineral raw materials for industrialization rather than beceuse of decreasing output of domestic mineral commodities in quantity. In terms of trade patterns, the 12 commodities concerned in this study can be classified into the following four groups. The 1st group - ores of lead and tungsten have only been exported without imports. The 2nd group - amorphous graphite, and pyrophyllite have mainly been exported but partly been imported. The 3rd group - kaolin, talc and crystalline graphite have equally been exported and imported, but quantity of imports have rapidly been increased with time. The 4th group - ores of iron, manganese and zinc have shifted from exports to imports during the industrialization, particularly owing to the initiation of iron and steel making by the Pohang Iron and Steel Company in the middle 1970' s and the new establishment of the Onsan Zinc Refinery in the late 1970' s. All of the 12 commodities under considerations were far above 100% in self-sufficiency rate before or in the early 1960' s. Recently, however, most of them have been declined to below 100% except for those of limestone (cement) and pyrophyllite. It is particularly serious to identify that the self-sufficiency rates of the three important metallic minerals, iron, copper and manganese ores in 1982 appeared to be 5.1%, 0.5%, and 0.01%, respectively. The average self-sufficiency rate of the total domestic minerals produced in 1982 was 14.4% (in value) for that year. Mining industry appeared to be extremely high in its intermediate demand rate whereas its intermediate input rate to be quite low indicating that mineral raw materials have been exerted strong forward linkage effects upon the other industries rather than backward linkage effects. In comparing the curves of increasing rates of demand-supply of several major minerals - iron ore, manganese ore, copper ore, limestone (cement), kaolin, and anthracite coal - with those of Gross Domestic Production and Economic Growth Rate drawn on every graph, it is clearly shown that the curves of increasing rates of demand-supply comprise around 6 to 7 periods of cycles which roughly harmonious with those of the curves of GDP and EGR, except for the curve of anthracite coal of which the configuration seems to have resulted from the (artificial) government's mineral policy rather than from economic free market mechanism. The harmonic feature of these curves well suggests that the increasing rates of demand-supply of major minerals have been significantly contributed to the GDP and EGR. In addition, the wider amplitudes of the iron, manganese and copper curves than those of the limestone (cement) and kaolin curves indicate that the contribution of the former, metallic commodities, has been greater than that of the latter, non-metallic commodities.

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Analysis of Combustion Characteristics and Diesel Exhaust Valve's Control with GT-Power 1-D Detail Model (GT-Power기반 디젤 배기밸브 제어모델 개발 및 연소 특성 해석)

  • Lee, Y.M.;Jo, I.S.;Kim, J.H.;Lee, J.W.
    • Journal of ILASS-Korea
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    • v.23 no.1
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    • pp.1-8
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    • 2018
  • In this study, the effects of variation in cam phasing and valve lift of exhaust valves by using Cam-in-Cam system on combustion and emission characteristics for diesel engine were investigated under GT-POWER simulation environment. This paper showed analytic result of combustion characteristics and diesel exhaust valve's control with GT-Power 1-D detail model. As a result, it was found that volumetric efficiency and IMEP were decreased as the exhaust valve opening and closing timing is advanced due to its internal EGR effects. Also, it was found that NOx emission were decreased as EVC timing was retarded. These show that the retarding the exhaust valve closing and opening while keeping the duration at constant can be effective for controlling AFR and mixing rate in diffusion combustion of diesel engine.

Experimental Investigation of Nano-sized Particulate Matter Emission Characteristics under Engine Operating Conditions from Common Rail Diesel Engine (커먼레일 디젤엔진의 운전조건이 나노크기 입자상 물질 배출특성에 미치는 영향에 관한 실험적 연구)

  • Lee, Hyung-Min;Myung, Cha-Lee;Park, Sim-Soo
    • Journal of Advanced Marine Engineering and Technology
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    • v.34 no.4
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    • pp.508-514
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    • 2010
  • The objective of this work presented here was experimental study of steadystate and cold start exhaust nano-sized particle characteristics from common rail diesel engine. The effect of the diesel oxidation catalyst (DOC) on the particle number reduction was insignificant, however, particle number concentration levels were reduced by 3 orders of magnitude into the downstream of diesel particulate filter (DPF). In high speed and load conditions, natural regeneration of trapped particle occurred inside DPF and it was referable to increase particle number concentration. As fuel injection timing was shifted BTDC $6^{\circ}CA$ to ATDC $4^{\circ}CA$, particle number concentration level was slightly reduced, however particle number and size was increased at ATDC $9^{\circ}CA$. Nucleation type particle reduced and accumulation type particle was increased on EGR condition.

Overexpression of Profilin 1 Inhibited Ovarian Tumor Cell Growth and Migration (Profilin-1 과발현에 의한 난소암 세포 성장 및 이동 저해 효능 연구)

  • Lee, Seung-Hoon
    • Journal of Life Science
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    • v.27 no.1
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    • pp.1-7
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    • 2017
  • Abnormal actin remodeling is a typical characteristic of tumor cells. Thymosin ${\beta}_{10}$ (TB10) and profilin-1 (PFN-1) are actin-binding proteins and essential regulators of actin polymerization. We previously showed that TB10 induced death in ovarian cancer cells by sequestering F-actin, but the underlying mechanisms of this induction have not been explored. In this study, we identified TB10 as a novel regulator of PFN-1 and demonstrated its novel function as a tumor suppressor in ovarian cancer cell lines. The present study investigated protein expression profiles through polyacrylamide gel electrophoresis (PAGE) and liquid chromatography-mass spectroscopy (LC-MS/MS) in SKOV3 cells, an ovarian cancer cell line, that were transiently transfected with TB10. PFN-1 was highly overexpressed in response to TB10, and overexpression of PFN-1 resulted in inhibition of cell proliferation and migration and promotion of cellular apoptosis in ovarian cancer cells. Furthermore, transiently transfected PFN-1 appeared to deactivate the Erk signaling pathway, followed by decreased expression of Elk-1 and Egr-1 in human ovarian cancer cells. Interestingly, PFN-1 did not affect the activation of Akt. The results demonstrated that PFN-1 induced apoptotic cell death and inhibited proliferation and migration in ovarian cancer cells, suggesting that PFN-1 may be valuable in anti-cancer therapy.