• Molecules and Cells
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• v.45 no.4
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• pp.180-192
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• 2022

Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator of nuclear receptors and other transcription factors. A general Ncoa6 knockout mouse was previously shown to be embryonic lethal, but we here generated liver-specific Ncoa6 knockout (Ncoa6 LKO) mice to investigate the metabolic function of NCOA6 in the liver. These Ncoa6 LKO mice exhibited similar blood glucose and insulin levels to wild type but showed improvements in glucose tolerance, insulin sensitivity, and pyruvate tolerance. The decrease in glucose production from pyruvate in these LKO mice was consistent with the abrogation of the fasting-stimulated induction of gluconeogenic genes, phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6pc). The forskolin-stimulated inductions of Pck1 and G6pc were also dramatically reduced in primary hepatocytes isolated from Ncoa6 LKO mice, whereas the expression levels of other gluconeogenic gene regulators, including cAMP response element binding protein (Creb), forkhead box protein O1 and peroxisome proliferator-activated receptor γ coactivator 1α, were unaltered in the LKO mouse livers. CREB phosphorylation via fasting or forskolin stimulation was normal in the livers and primary hepatocytes of the LKO mice. Notably, it was observed that CREB interacts with NCOA6. The transcriptional activity of CREB was found to be enhanced by NCOA6 in the context of Pck1 and G6pc promoters. NCOA6-dependent augmentation was abolished in cAMP response element (CRE) mutant promoters of the Pck1 and G6pc genes. Our present results suggest that NCOA6 regulates hepatic gluconeogenesis by modulating glucagon/cAMP-dependent gluconeogenic gene transcription through an interaction with CREB.

• Journal of Life Science
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• v.15 no.6 s.73
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• pp.928-934
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• 2005

ATF2 is a cellular transcription factor which belongs to the CREB/ATF class and it is leucine zipper protein which generally binds to DNA as dimers. This paper presents the procedure for subcloning the ATF2 gene and the results of experiment used the expressed ATF2. The pET expression vector was used since it produced 6xHis fusion protein for easy purification using affinity column. The Nickel chelating chromatography was used for Purifying the expressed ATE2 from E- codi BL2l. Subsequen시y In vitro binding pull-down assay showed the binding specificity of ATF2 with AP-1 family factors such as BATF, c-Fos, c-Jun and ATF2 itselgf. ATF2 forms homodimer as well as strong heterodimer with BATF. It also forms stable dimer with c-Jun but barely binds with c-Fos.

• Molecules and Cells
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• v.41 no.7
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• pp.695-702
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• 2018

The inner ear is a complex sensory organ responsible for hearing and balance. Formation of the inner ear is dependent on tight regulation of spatial and temporal expression of genes that direct a series of developmental processes. Recently, epigenetic regulation has emerged as a crucial regulator of the development of various organs. However, what roles higher-order chromatin organization and its regulator molecules play in inner ear development are unclear. CCCTC-binding factor (CTCF) is a highly conserved 11-zinc finger protein that regulates the three-dimensional architecture of chromatin, and is involved in various gene regulation processes. To delineate the role of CTCF in inner ear development, the present study investigated inner ear-specific Ctcf knockout mouse embryos (Pax2-Cre; $Ctcf^{fl/fl}$). The loss of Ctcf resulted in multiple defects of inner ear development and severely compromised otic neurogenesis, which was partly due to a loss of Neurog1 expression. Furthermore, reduced Neurog1 gene expression by CTCF knockdown was found to be associated with changes in histone modification at the gene's promoter, as well as its upstream enhancer. The results of the present study demonstrate that CTCF plays an essential role in otic neurogenesis by modulating histone modification in the Neurog1 locus.

• Journal of Acupuncture Research
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• v.26 no.5
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• pp.39-47
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• 2009

목적 : 정상 췌장조직 속에 존재하는 췌장 소도세포들을 파괴시켜 고혈당을 유발시키고 복령 물추출물로 약침을 시술하여 췌장 조직의 보호효과와 항당뇨 효과를 살펴보고자 실험을 진행하였다. 방법 : 5주령의 Sprague-Dawley rat을 통제된 실험실 환경에 적응시킨 후 1주일간 복령약침액(125mg/kg 복령약침군 및 250mg/kg 복령약침군)을 좌우 신수($BL_{23}$)에 교대로 각각 피하에 약침하고 streptozotocin을 복강내 주사하여 3일 후 diabetes mellitus 유도 정도를 평가하고 2주일간 추가 치료를 진행 한 뒤, 혈액지표(plasma glucose, insulin, TG, TC, NEFA, sGOT, sGPT, ALP, BUN, CRE)와 췌장조직의 형태학적 분석 및 염증 관련 단백질의 발현을 평가하였다. 결과 : 복령약침군(125mg/kg 복령약침군 및 250mg/kg 복령약침군)에서 insulin과 triglyceride, NEFA 수치가 유의하게 감소하였으며 간 기능 효소수치인 sGOT가 감소하는 경향을 나타내었으나, 신장기능지수는 유의한 감소를 나타내지 않았다. 특히 250mg/kg 복령약침군에서 streptozotocin 투여로 인한 pancreatic islet의 형태학적 변성이 현저하게 개선되었다. Western blot 결과 JNK-2, P-JNK-2, P-JNK-1, ERK1/2 및 phosphorylated ERK1의 발현이 감소되었다. 결론 : 복령약침이 고인슐린혈증과 고지질질혈증을 개선시키고 streptozotocin에 의한 pancreatic islet의 파괴를 억제하며, 이는 inflammation-related transcription factor인 NF-kB와도 관련이 있는 것으로 판단된다. 향후 복령약침의 항당뇨 효과와 그 기전에 관한 추가 연구가 필요할 것으로 사료된다

• Korean Journal of Remote Sensing
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• v.34 no.2_1
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• pp.237-248
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• 2018

The vertical distribution of hydrometeor before precipitation near the cloud base has been analyzed using a scanning lidar, rawinsonde data, and Cloud-Resolving Storm Simulator (CReSS). This study mostly focuses on 13 Desember 2016 only. The typical synoptic pattern of lake-effect snowstorm induced easterly in the Yeongdong region. Clouds generated due to high temperature difference between 850 hPa and sea surface (SST) penentrated in the Yeongdong region along with northerly and northeasterly, which eventually resulted precipitation. The cloud base height before the precipitation changed from 750 m to 1,280 m, which was in agreement with that from ceilometer at Sokcho. However, ceilometer tended to detect the cloud base 50 m ~ 100 m below strong signal of lidar backscattering coefficient. As a result, the depolarization ratio increased vertically while the backscattering coefficient decreased about 1,010 m~1,200 m above the ground. Lidar signal might be interpreted to be attenuated with the penetration depth of the cloud layer with of nonspherical hydrometeor (snow, ice cloud). An increase in backscattering signal and a decrease in depolarization ratio occured in the layer of 800 to 1,010 m, probably being associated with an increase in non-spherical particles. There seemed to be a shallow liquid layer with a low depolarization ratio (<0.1) in the layer of 850~900 m. As the altitude increases in the 680 m~850 m, the backscattering coefficient and depolarization ratio increase at the same time. In this range of height, the maximum value (0.6) is displayed. Such a result can be inferred that the nonspherical hydrometeor are distributed by a low density. At this time, the depolarization ratio and the backscattering coefficient did not increase under observed melting layer of 680 m. The lidar has a disadvantage that it is difficult for its beam to penetrate deep into clouds due to attenuation problem. However it is promising to distinguish hydrometeor morphology by utilizing the depolarization ratio and the backscattering coefficient, since its vertical high resolution (2.5 m) enable us to analyze detailed cloud microphysics. It would contribute to understanding cloud microphysics of cold clouds and snowfall when remote sensings including lidar, radar, and in-situ measurements could be timely utilized altogether.

• Biomedical Science Letters
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• v.13 no.4
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• pp.287-291
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• 2007

The factors and mechanisms by infection of Oriental Tsutsugamushi caused disease are not well understood. The onset of tsutsugamushi disease is characterized by chilliness, fever, malaise, headache and generalized aching. Infection of tsutsugamushi is the cause of impairment of function of a major organ often complicate the picture and immediately change the prognosis for the worse. Tsutsugamushi disease is reported that this disease is characterized by the histopathogenesis of liver, kidney, heart, and lung, but the variation of biochemical components in serum of tsutsugamushi disease patient are not clear. We analyzed total protein (TP), albumin (AL), aspartic aminotranferase (AST), alanine aminotransferase (ALT), alkaline phosphotase (ALP), urea nitrogen (UN), creatinine (CRE), glucose (GLD), cholesterol (CHOL) and total bilirubin (TB) in sera of patients with tsutsugamushi disease. In comparison with reference, total protein and albumin were abnormally decreased in 19.6% and 39.2% of patients, respectively. AST, ALT, ALP, creatinine, UN, glucose, cholesterol and total bilirubin were abnormally increased in 94.1 %, 72.5%, 25.5%, 15.7%, 9.8%, 62.7%, 25.5% and 6.0% of patients, respectively. The patients showed abnormal relative rate of protein electrophoretic fractions to total protein in serum compared to them of reference were 43.1% (albumin), 12.9% ($\alpha_1$-globulin), 58.8% ($\alpha_2$-globulin), 60.8% ($\beta$-globulin) and 70.6% ($\gamma$-globulin), respectively. These data suggest that infection of Oriental Tsutsugamushi causes impairment of function of a major organ and abnormal serum protein electrophoresis fractions to tsutsugamushi patients.

• Journal of the korean academy of Pediatric Dentistry
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• v.45 no.2
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• pp.144-153
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• 2018

The aim of this study was to understand the roles of Sonic Hedgehog (SHH) signaling during tooth root and periodontium formation. In this study, we generated the dental mesenchyme-specific Smoothened (Smo) activated/inactivated mice with the activity of Cre recombinase under the control of osteocalcin promoter. In the Smo activated mutant molar sections at the postnatal 28 days, we found extremely thin root dentin and widened pulp chamber. Picrosirius red staining showed loosely arranged fibers in the periodontal space and decreased cellular cementum with some root resorption. Immunohistochemical staining showed less localization of matrix proteins such as Bsp, Dmp1, Pstn, and Ank in the cementum, periodontal ligament, and/or cementoblast. In the Smo inactivated mutant mouse, there was not any remarkable differences in the localization of these matrix proteins compared with the wild type. These findings suggest that adequate suppressing regulation of SHH signaling is required in the development of tooth root and periodontium.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.311-320
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• 2021

Accumulation of reactive oxygen species (ROS) is associated with the development of various diseases. However, the molecular mechanisms underlying oxidative stress that lead to such diseases like autosomal dominant polycystic kidney disease (ADPKD) remain unclear. Here, we observed that oxidative stress markers were increased in Pkd1f/f:HoxB7-Cre mice. Forkhead transcription factors of the O class (FOXOs) are known key regulators of the oxidative stress response, which have been observed with the expression of FoxO3a in an ADPKD mouse model in the present study. An integrated analysis of two datasets for differentially expressed miRNA, such as miRNA sequencing analysis of Pkd1 conditional knockout mice and microarray analysis of samples from ADPKD patients, showed that miR-132-3p was a key regulator of FOXO3a in ADPKD. miR-132-3p was significantly upregulated in ADPKD which directly targeted FOXO3 in both mouse and human cell lines. Interestingly, the mitochondrial gene Gatm was downregulated in ADPKD which led to a decreased inhibition of Foxo3. Overexpression of miR-132-3p coupled with knockdown of Foxo3 and Gatm increased ROS and accelerated cyst formation in 3D culture. This study reveals a novel mechanism involving miR-132-3p, Foxo3, and Gatm that is associated with the oxidative stress that occurs during cystogenesis in ADPKD.

• BMB Reports
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• v.54 no.6
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• pp.317-322
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• 2021

CCCTC-binding factor (CTCF), a zinc finger protein, is a transcription factor and regulator of chromatin structure. Forebrain excitatory neuron-specific CTCF deficiency contributes to inflammation via enhanced transcription of inflammation-related genes in the cortex and hippocampus. However, little is known about the long-term effect of CTCF deficiency on postnatal neurons, astrocytes, or microglia in the hippocampus of adult mice. To address this, we knocked out the Ctcf gene in forebrain glutamatergic neurons (Ctcf cKO) by crossing Ctcf-floxed mice with Camk2a-Cre mice and examined the hippocampi of 7.5-10-month-old male mice using immunofluorescence microscopy. We found obvious neuronal cell death and reactive gliosis in the hippocampal cornu ammonis (CA)1 in 7.5-10-month-old cKO mice. Prominent rod-shaped microglia that participate in immune surveillance were observed in the stratum pyramidale and radiatum layer, indicating a potential increase in inflammatory mediators released by hippocampal neurons. Although neuronal loss was not observed in CA3, and dentate gyrus (DG) CTCF depletion induced a significant increase in the number of microglia in the stratum oriens of CA3 and reactive microgliosis and astrogliosis in the molecular layer and hilus of the DG in 7.5-10-month-old cKO mice. These results suggest that long-term Ctcf deletion from forebrain excitatory neurons may contribute to reactive gliosis induced by neuronal damage and consequent neuronal loss in the hippocampal CA1, DG, and CA3 in sequence over 7 months of age.

• Molecules and Cells
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• v.23 no.1
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• pp.23-29
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• 2007

Cyclic AMP-responsive element binding protein (CREB) is known to be associated with angiogenesis. In the present study we investigated the possible role of CREB in the expression of vascular endothelial growth factor (VEGF) by mouse macrophages. Over-expression of CREB increased VEGF secretion by cells of the RAW264.7 mouse macrophage cell line. It also increased the promoter activity of a mouse reporter driven by the VEGF promoter, while a dominant negative CREB (DN-CREB) abrogated the activity, suggesting that CREB mediates VEGF transcription. Forskolin, an adenylyl cyclase activator, stimulated VEGF transcription, and the PKA inhibitor H89 abolished this effect. IFN-${\gamma}$, a potent cytokine, stimulated VEGF expression only in part through the PKA-CREB pathway. These results indicate that PKA phosphorylates CREB and so induces VEGF gene expression. An analysis of mutant promoters revealed that one of the putative CREB responsive elements (CREs), at -399 ~ -388 in the promoter, is critical for CREB-mediated VEGF promoter activity, and the significance of this CRE was confirmed by chromatin immunoprecipitation assays.