• Clinical and Experimental Reproductive Medicine
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• v.26 no.3
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• pp.383-387
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• 1999

Objective: There is increasing evidence for the expression of rat in gene in several extrapituitary sites including testis and ovary. We also have demonstrated that the local LH expression in the rat epididymis and uterus, the major accessory sex organs in male and female reproductive system, respectively. Design: The present study was undertaken to elucidate whether the gene for LH receptor is expressed in rat uterus and whether the expressions of uterine LH and its receptor are differentially regulated during estrous cycle. Presence of the transcripts for rat LH receptor in the rat uterine tissue were confirmed by touchdown reverse transcription-polymerase chain reaction (RT-PCR). Results: In $LH{\beta}$ semi-quantitative RT-PCR, the highest expression level was shown in estrus stage. The level of ill receptor transcripts was also fluctuated during estrous cycle. In ovariectomized rats (OVX + Oil), the expressions of both uterine LH and LH-R were markedly reduced when compared to those from normal rats. Supplement with estradiol $17{\beta}$ to the ovariectomized rats (OVX + $E_2$) restored the expression levels of LH and its receptor to the levels in uteri from normal rats. Conclusion: Our findings indicated that 1) LH and its receptor gene are expressed in the rat uterus from cycling rats, 2) the expression of uterine LH and its receptor is mainly, if not all, under the control of ovarian sex steroid(s). These results suggested that the uterine LH may act as a local regulator with auto and/or paracrine manner, though the posibility that the pituitary LH may act directly on the regulation of uterine functions could not be discarded.

• Genomics & Informatics
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• v.3 no.3
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• pp.74-79
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• 2005

The H19 gene, located at human chromosome 11p15.5, is imprinted in most normal human tissues. However, imprinting is often lost in tumors suggesting H19 is a putative tumor suppressor. We analyzed the single nucleotide polymorphisms (SNPs) of a 16 kb region that includes the H19 gene and its imprinting control region (ICR) in the Korean population. To identify SNPs, we directly sequenced this region in 18 Korean subjects. We identified 64 SNPs, of which 7 were in the exons of H19, 2 were in the introns, 14 were in the 3' intergenic region and 41 were in the 5' intergenic region. Of the 64 SNPs, 21 had not previously been reported and thus appear to be unique to the Korean population. The identified SNPs of H19 in the Korean population may eventually be useful as genetic markers associated with various diseases. In this study, 7 of the 64 identified SNPs were at CTCF binding sites in the ICR and may affect regulation of H19 gene imprinting. Thus, several genetic variations of the H19 gene may be important markers in human diseases that involve genomic imprinting, including cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.533-538
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• 2016

Angiogenesis plays an essential role in embryo development, tissue repair, inflammatory diseases, and tumor growth. In the present study, we showed that endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice that lack eNOS showed growth retardation, and retinal vessel development was significantly delayed. In addition, the number of tip cells and filopodia length were significantly reduced in mice lacking eNOS. Retinal endothelial cell proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced endothelial cell sprouting was significantly reduced in aortic vessels isolated from eNOS-deficient mice. Finally, pericyte recruitment to endothelial cells and vascular smooth muscle cell coverage to blood vessels were attenuated in mice lacking eNOS. Taken together, we suggest that the endothelial cell function and blood vessel maturation are regulated by eNOS during retinal angiogenesis.

• Biomolecules & Therapeutics
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• v.22 no.6
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• pp.525-531
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• 2014

In the present study, we investigated whether apigenin significantly affects tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced production and gene expression of MUC5AC mucin in airway epithelial cells. Confluent NCI-H292 cells were pretreated with apigenin for 30 min and then stimulated with TNF-${\alpha}$ for 24 h or the indicated periods. The MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription - polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Apigenin significantly inhibited MUC5AC mucin production and down-regulated MUC5AC gene expression induced by TNF-${\alpha}$ in NCI-H292 cells. To elucidate the action mechanism of apigenin, effect of apigenin on TNF-${\alpha}$-induced nuclear factor kappa B (NF-${\kappa}B$) signaling pathway was also investigated by western blot analysis. Apigenin inhibited NF-${\kappa}B$ activation induced by TNF-${\alpha}$. Inhibition of inhibitory kappa B kinase (IKK) by apigenin led to the suppression of inhibitory kappa B alpha ($I{\kappa}B{\alpha}$) phosphorylation and degradation, p65 nuclear translocation. This, in turn, led to the down-regulation of MUC5AC protein production in NCI-H292 cells. Apigenin also has an influence on upstream signaling of IKK because it inhibited the expression of adaptor protein, receptor interacting protein 1 (RIP1). These results suggest that apigenin can regulate the production and gene expression of mucin through regulating NF-${\kappa}B$ signaling pathway in airway epithelial cells.

• Proceedings of the Zoological Society Korea Conference
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• 1999.10b
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• pp.31-31
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• 1999

Characterization of mutant mice has been utilized as an animal model for the study of human inherited diseases. In addition to the pathogenesis stduy using the mutant mice, the mice have been used for the identification of the genes causing the phenotypes. Functional cloning and positional cloning are two approaches, depending on the phenotypes of the mutant mice. Though it takes a long time positional cloning has been well used to identify the gene of which function can not be presumed from the mouse phenotype. Recently by the advance of the molecular tools and the human genome project close to 10,000 genetic markers are developed to make the procedure faster. We obtained a new mutant mouse, sims, spontaneously arose and the affected mouse has a mild tremor and seizure was observed. Homozygote in either sex is sterile since uterus growth in female and seminal vesicle in male are not induced for the growth in puberty, implying the abnormal hormonal regulation during puberty. Supporting this, there is no detectable testosterone in the serum of the mutant male and the brain of the mutant is 30% heavier than littermate. To identify the location of the mutated gene, intraspecies cross to CAST/Ei was carried out and the 37 affected mice was analyzed for the linkage. The gene was mapped on chromosome 18, 20 cM from the centromere. More than 500 F2 progenies have been analyzed for the linkage and the locus becomes narrow within 3cM between Egrl and Fgf gene.f gene.

• Molecules and Cells
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• v.42 no.2
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• pp.123-134
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• 2019

Lysophosphatidic acid (LPA) is an endogenous lysophospholipid with signaling properties outside of the cell and it signals through specific G protein-coupled receptors, known as $LPA_{1-6}$. For one of its receptors, $LPA_1$ (gene name Lpar1), details on the cis-acting elements for transcriptional control have not been defined. Using 5'RACE analysis, we report the identification of an alternative transcription start site of mouse Lpar1 and characterize approximately 3,500 bp of non-coding flanking sequence 5' of mouse Lpar1 gene for promoter activity. Transient transfection of cells derived from mouse neocortical neuroblasts with constructs from the 5' regions of mouse Lpar1 gene revealed the region between -248 to +225 serving as the basal promoter for Lpar1. This region also lacks a TATA box. For the region between -761 to -248, a negative regulatory element affected the basal expression of Lpar1. This region has three E-box sequences and mutagenesis of these E-boxes, followed by transient expression, demonstrated that two of the E-boxes act as negative modulators of Lpar1. One of these E-box sequences bound the HeLa E-box binding protein (HEB), and modulation of HEB levels in the transfected cells regulated the transcription of the reporter gene. Based on our data, we propose that HEB may be required for a proper regulation of Lpar1 expression in the embryonic neocortical neuroblast cells and to affect its function in both normal brain development and disease settings.

• Toxicological Research
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• v.35 no.3
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• pp.257-270
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• 2019

Silver nanoparticles (AgNPs) have been widely used in a variety of applications in innovative development; consequently, people are more exposed to this particle. Growing concern about toxicity from AgNP exposure has attracted greater attention, while questions about nanosilver-responsive genes and consequences for human health remain unanswered. By considering early detection and prevention of nanotoxicology at the genetic level, this study aimed to identify 1) changes in gene expression levels that could be potential indicators for AgNP toxicity and 2) morphological phenotypes correlating to toxicity of HepG2 cells. To detect possible nanosilver-responsive genes in xenogenic targeted organs, a comprehensive systematic literature review of changes in gene expression in HepG2 cells after AgNP exposure and in silico method, connection up- and down-regulation expression analysis of microarrays (CU-DREAM), were performed. In addition, cells were extracted and processed for transmission electron microscopy to examine ultrastructural alterations. From the Gene Expression Omnibus (GEO) Series database, we selected genes that were up- and down-regulated in AgNPs, but not up- and down-regulated in silver ion exposed cells, as nanosilver-responsive genes. HepG2 cells in the AgNP-treated group showed distinct ultrastructural alterations. Our results suggested potential representative gene data after AgNPs exposure provide insight into assessment and prediction of toxicity from nanosilver exposure.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.22 no.5
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• pp.460-469
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• 2019

Purpose: The ${\beta}3-adrenergic$ receptor (ADRB3) is expressed in visceral adipose tissue and has been speculated to contribute to lipolysis, energy metabolism, and regulation of the metabolic rate. In this study, we aimed to investigate the association of polymorphism of the ADRB3 gene with the sex of children with obesity and related pathologies. Methods: ADRB3 gene trp64arg genotyping was conducted in 441 children aged 6-18 years. Among these subjects, 264 were obese (103 boys; 161 girls) and 179 were of normal weight (81 boys; 98 girls). In the obese group, fasting lipids, glucose and insulin levels, and blood pressure were measured. Metabolic syndrome (MS) was defined according to the modified World Health Organization criteria adapted for children. Results: The frequency of trp64arg genotype was similar in obese and normal weight children. In obese children, serum lipid, glucose, and insulin levels; homeostasis model assessment of insulin resistance (HOMA-IR) scores; and MS were not different between arg allele carriers (trp64arg) and noncarriers (trp64trp). In 264 obese children, genetic analysis results revealed that the arg allele carriers were significantly higher in girls than in boys (p=0.001). In the normal weight group, no statistically significant difference was found between genotypes of boys and girls (p=0.771). Conclusion: Trp64arg polymorphism of the ADRB3 gene was not associated with obesity and MS in Turkish children and adolescents. Although no relationships were observed between the genotypes and lipids, glucose/insulin levels, or HOMA-IR, the presence of trp64arg variant was frequent in obese girls, which can lead to weight gain as well as difficulty in losing weight in women.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.2
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• pp.119-124
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• 2022

Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are typical opportunistic pathogens. Moreover, these bacteria are known to possess multidrug-resistant (MDR) properties. This study investigates the antimicrobial activity of six fermented products, which have varying efficacies against P. aeruginosa, E. coli, and S. aureus. To identify novel candidate genes, differential expression analysis was performed using an annealing control primer. In the disk diffusion method, Fig vinegar (FV) and Diospyros kaki Thunb vinegar (DTV) showed the greatest increase in inhibition compared to other fermented products, whereas fermented Korean traditional nature herb (FKTNH) had no antibacterial effect. This study identified down-regulation of Escherichia coli O157:H7 ompW gene for outer membrane protein W, whereas gene for synthetic construct Lao1 gene for L-amino acid oxidase were up-regulated in E. coli treated with 5% FV. Consuming fermented vinegar helps prevent bacterial infections. Especially, FV and DTV are potentially useful alternative natural products for multidrug resistance. Furthermore, both are expected to be used as effective natural antimicrobial agents, such as disinfectants.

• Molecules and Cells
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• v.45 no.5
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• pp.306-316
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• 2022

Chronic stress contributes to the risk of developing depression; the habenula, a nucleus in epithalamus, is associated with many neuropsychiatric disorders. Using genome-wide gene expression analysis, we analyzed the transcriptome of the habenula in rats exposed to chronic restraint stress for 14 days. We identified 379 differentially expressed genes (DEGs) that were affected by chronic stress. These genes were enriched in neuroactive ligand-receptor interaction, the cAMP (cyclic adenosine monophosphate) signaling pathway, circadian entrainment, and synaptic signaling from the Kyoto Encyclopedia of Genes and Genomes pathway analysis and responded to corticosteroids, positive regulation of lipid transport, anterograde trans-synaptic signaling, and chemical synapse transmission from the Gene Ontology analysis. Based on protein-protein interaction network analysis of the DEGs, we identified neuroactive ligand-receptor interactions, circadian entrainment, and cholinergic synapse-related subclusters. Additionally, cell type and habenular regional expression of DEGs, evaluated using a recently published single-cell RNA sequencing study (GSE137478), strongly suggest that DEGs related to neuroactive ligand-receptor interaction and trans-synaptic signaling are highly enriched in medial habenular neurons. Taken together, our findings provide a valuable set of molecular targets that may play important roles in mediating the habenular response to stress and the onset of chronic stress-induced depressive behaviors.