• Title/Summary/Keyword: down-regulation

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RNA-Seq explores the functional role of the fibroblast growth factor 10 gene in bovine adipocytes differentiation

  • Nurgulsim Kaster;Rajwali Khan;Ijaz Ahmad;Kazhgaliyev Nurlybay Zhigerbayevich;Imbay Seisembay;Akhmetbekov Nurbolat;Shaikenova Kymbat Hamitovna;Omarova Karlygash Mirambekovna;Makhanbetova Aizhan Bekbolatovna;Tlegen Garipovich Amangaliyev;Ateikhan Bolatbek;Titanov Zhanat Yeginbaevich;Shakoor Ahmad;Zan Linsen;Begenova Ainagul Baibolsynovna
    • Animal Bioscience
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    • v.37 no.5
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    • pp.929-943
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    • 2024
  • Objective: The present study was executed to explore the molecular mechanism of fibroblast growth factor 10 (FGF10) gene in bovine adipogenesis. Methods: The bovine FGF10 gene was overexpressed through Ad-FGF10 or inhibited through siFGF10 and their negative control (NC) in bovine adipocytes, and the multiplicity of infection, transfection efficiency, interference efficiency were evaluated through quantitative real-time polymerase chain reaction, western blotting and fluorescence microscopy. The lipid droplets, triglycerides (TG) content and the expression levels of adipogenic marker genes were measured during preadipocytes differentiation. The differentially expressed genes were explored through deep RNA sequencing. Results: The highest mRNA level was found in omasum, subcutaneous fat, and intramuscular fat. Moreover, the highest mRNA level was found in adipocytes at day 4 of differentiation. The results of red-oil o staining showed that overexpression (Ad-FGF10) of the FGF10 gene significantly (p<0.05) reduced the lipid droplets and TG content, and their down-regulation (siFGF10) increased the measurement of lipid droplets and TG in differentiated bovine adipocytes. Furthermore, the overexpression of the FGF10 gene down regulated the mRNA levels of adipogenic marker genes such as CCAAT enhancer binding protein alpha (C/EBPα), fatty acid binding protein (FABP4), peroxisome proliferator-activated receptor-γ (PPARγ), lipoprotein lipase (LPL), and Fas cell surface death receptor (FAS), similarly, down-regulation of the FGF10 gene enriched the mRNA levels of C/EBPα, PPARγ, FABP4, and LPL genes (p<0.01). Additionally, the protein levels of PPARγ and FABP4 were reduced (p<0.05) in adipocytes infected with Ad-FGF10 gene and enriched in adipocytes transfected with siFGF10. Moreover, a total of 1,774 differentially expressed genes (DEGs) including 157 up regulated and 1,617 down regulated genes were explored in adipocytes infected with Ad-FGF10 or Ad-NC through deep RNA-sequencing. The top Kyoto encyclopedia of genes and genomes pathways regulated through DEGs were the PPAR signaling pathway, cell cycle, base excision repair, DNA replication, apoptosis, and regulation of lipolysis in adipocytes. Conclusion: Therefore, we can conclude that the FGF10 gene is a negative regulator of bovine adipogenesis and could be used as a candidate gene in marker-assisted selection.

The Trend of Competitive Structure in Telecommunications Industry : The Case of Voice Fixed and Mobile Service

  • Kim, Moon-Soo;Kim, Byung-Woon
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.34 no.1B
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    • pp.34-46
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    • 2009
  • The remarkable growth of Korean telecommunication market has based on the introduction of competition as well as mobile technology like CDMA. It was well Down that such a conspicuous growth has been towed by mobile service rather than fixed telephone service. In telecommunications service the number of subscribers to mobile was over 40 millions in 2006 and also, while the traffic amount of fixed telephone has been more decreased, that of mobile, which already outnumbers the fixed, has been constantly increased and will be much more in future. It will accelerate the substitution of access and call demand of fixed service by mobile. This change of technology and demand does affect directly the market performance of telecommunications. And regulation has also an effect on market structure, which finally affects on market performance. In this paper we suppose the fixed and mobile telecommunications services are in a same industry. After reviewing the relations among the demand, cost, charge structure and revenue structure in the one fixed and mobile telecommunications market using the framework of an industrial structure analysis, we discuss the current issues of telecommunications regulation and implications for the future regulation.

E3 ubiquitin ligases and deubiquitinases as modulators of TRAIL-mediated extrinsic apoptotic signaling pathway

  • Woo, Seon Min;Kwon, Taeg Kyu
    • BMB Reports
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    • v.52 no.2
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    • pp.119-126
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    • 2019
  • The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) initiates the extrinsic apoptotic pathway through formation of the death-inducing signaling complex (DISC), followed by activation of effector caspases. TRAIL receptors are composed of death receptors (DR4 and DR5), decoy receptors (DcR1 and DcR2), and osteoprotegerin. Among them, only DRs activate apoptotic signaling by TRAIL. Since the levels of DR expressions are higher in cancer cells than in normal cells, TRAIL selectively activates apoptotic signaling pathway in cancer cells. However, multiple mechanisms, including down-regulation of DR expression and pro-apoptotic proteins, and up-regulation of anti-apoptotic proteins, make cancer cells TRAIL-resistant. Therefore, many researchers have investigated strategies to overcome TRAIL resistance. In this review, we focus on protein regulation in relation to extrinsic apoptotic signaling pathways via ubiquitination. The ubiquitin proteasome system (UPS) is an important process in control of protein degradation and stabilization, and regulates proliferation and apoptosis in cancer cells. The level of ubiquitination of proteins is determined by the balance of E3 ubiquitin ligases and deubiquitinases (DUBs), which determine protein stability. Regulation of the UPS may be an attractive target for enhancement of TRAIL-induced apoptosis. Our review provides insight to increasing sensitivity to TRAIL-mediated apoptosis through control of post-translational protein expression.

The Politics of Scale: The Social and Political Construction of Geographical Scale in Korean Housing Politics (스케일의 정치: 한국 주택 정치에서의 지리적 스케일의 사회적.정치적 구성)

  • Ryu, Yeon-Taek
    • Journal of the Korean Geographical Society
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    • v.42 no.5
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    • pp.691-709
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    • 2007
  • This paper investigates the social and political construction of geographical scale in conjunction with Korean housing politics. Recently, attention has been drawn to the issue of the social and political construction of geographical scale. Spatial scales have increasingly been regarded as socially constructed and politically contested rather than ontologically pregiven or fixed. The scale literature has paid attention to how different spatial scales can be used or articulated in social movements, with an emphasis on 'up-scaling' and 'scales of activism' rather than 'down-scaling' and 'scales of regulation.' Furthermore, the scale literature has focused on the aspect of empowerment. However, it is worthwhile to examine how scale-especially 'down-scaling' and 'scales of regulation'-can be used not only for marginalizing or excluding unprivileged social groups, but also for controlling the (re)production of space, including housing space. Under a regulatory regime, the Korean central government gained more control over the (re)production of housing space at geographical multi-scales by means of 'jumping scales,' specifically 'down-scaling.' The Korean central government has increasingly obtained the capacity to 'jump scales' by using not only multiscalar strategies for housing developments, but also taking advantage of various scales of institutional networking among the central and local governments, quasi-governmental institutions, and Chaebols, across the state. Traditionally, scale has been regarded as an analytical spatial unit or category. However, scale can be seen as means of inclusion(and exclusion) and legitimation. Choosing institutions to include or exclude cannot be separated from the choices and range of spatial scale, and is closely connected to 'scale spatiality of politics.' Facilitating different forms of 'scales of regulation,' the Korean central government included Chaebols and upper- and middle-income groups for the legitimization of housing projects, but excluded local-scale grassroots organizations and unprivileged social groups as decision-makers.

The Legislation of SI Distinction & Separation in Long-Life Housing (장수명 공동주택에서의 SI구분 및 분리기준에 관한 법제화 방향)

  • Chung, Joon-Soo;Kim, Soo-Am
    • Proceeding of Spring/Autumn Annual Conference of KHA
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    • 2009.04a
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    • pp.222-225
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    • 2009
  • The apartment housing in Korea has been rapidly constructed by adapting the most suitable construction methods as like wall structure, wet and united construction. But most of short-lived equipments usually filled in the structure which has longer life, and it causes not only to make difficult coping with the deterioration of equipments but also to let buildings remained deteriorate themselves. The buildings can be remodelled to slow down the terms of deterioration or reconstructed to give a new life of themselves, although the disposal of wastes or the lack of natural resources still be problems and unsolved that can occurred in pulling down and reconstructing the buildings. Furthermore, it is the time to need keeping with worldwide trends and movements as like sustainability or 'green growth' movements based on low carbon emissions. The researches for Long-Life Housing apartments which has durability and variation have been advanced up to now. Long-Life Housing apartments can separate their structures from equipments and interior or exterior materials of buildings. Therefore equipments or materials of buildings can be easily repaired and replaced with new ones, even if they are deteriorated themselves. Also, the construction process of Long-Life Housing apartments can be independent from the matter of proprietary rights, terms of durability, decision rights and so on. 'The law of Possession and Management of Collective Building' and the 'Regulation of Management of Collective Building' established by each local governments are already legislated for declaring the rights of using and ownership, responsibilities of each parts of apartment buildings. These laws and regulations classify the ownership of each parts of apartment buildings, and divide the ownership with public possession and exclusive possession. Therefore, this study will conduct comparative analysis between 'The law of Possession and Management of Collective Building' and 'the Regulation of Management of Collective Building' and find problems which can be occurred in future construction of Long-Life Housing apartments. It will be helpful to revise laws and regulations.

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A Long Non-Coding RNA snaR Contributes to 5-Fluorouracil Resistance in Human Colon Cancer Cells

  • Lee, Heejin;Kim, Chongtae;Ku, Ja-Lok;Kim, Wook;Kim Yoon, Sungjoo;Kuh, Hyo-Jeong;Lee, Jeong-Hwa;Nam, Suk Woo;Lee, Eun Kyung
    • Molecules and Cells
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    • v.37 no.7
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    • pp.540-546
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    • 2014
  • Several types of genetic and epigenetic regulation have been implicated in the development of drug resistance, one significant challenge for cancer therapy. Although changes in the expression of non-coding RNA are also responsible for drug resistance, the specific identities and roles of them remain to be elucidated. Long non-coding RNAs (lncRNAs) are a type of ncRNA (> 200 nt) that influence the regulation of gene expression in various ways. In this study, we aimed to identify differentially expressed lncRNAs in 5-fluorouracil-resistant colon cancer cells. Using two pairs of 5-FU-resistant cells derived from the human colon cancer cell lines SNU-C4 and SNU-C5, we analyzed the expression of 90 lncRNAs by qPCR-based profiling and found that 19 and 23 lncRNAs were differentially expressed in SNU-C4R and SNU-C5R cells, respectively. We confirmed that snaR and BACE1AS were down-regulated in resistant cells. To further investigate the effects of snaR on cell growth, cell viability and cell cycle were analyzed after transfection of siRNAs targeting snaR. Down-regulation of snaR decreased cell death after 5-FU treatment, which indicates that snaR loss decreases in vitro sensitivity to 5-FU. Our results provide an important insight into the involvement of lncRNAs in 5-FU resistance in colon cancer cells.

A Homeotic Gene, Hoxc8, Regulates the Expression of Proliferating Cell Nuclear Antigen in NIH3T3 Cell

  • Min, Hye-Hyun;Kang, Myeng-Mo;Kim, Myoung-Hee
    • Biomedical Science Letters
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    • v.13 no.3
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    • pp.239-244
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    • 2007
  • Hoxc8 is one of the homeotic developmental control genes regulating the expression of many downstream target genes, through which animal body pattern is established during embryonic development. In previous proteomics analysis, proliferating cell nuclear antigen (PCNA) which is also known as cyclin, has been implied to be regulated by Hoxc8 in F9 murine embryonic teratocarcinoma cell. When the 5' upstream region of PCNA was analyzed, it turned out to contain 20 Hox core binding sites (ATTA) in about 1.17 kbp (kilo base pairs) region ($-520{\sim}-1690$). In order to test whether this region is responsible for Hoxc8 regulation, the upstream 2.3 kbp fragment of PCNA was amplified through PCR and then cloned into the pGL3 basic vector containing a luciferase gene as a reporter. When the luciferase activity was measured in the presence of effector plasmid (pcDNA : c8) expressing murine Hoxc8, the PCNA promoter driven reporter activity was reduced. To confirm whether this reduction is due to the Hoxc8 protein, the siRNA against Hoxc8 (5'-GUA UCA GAC CUU GGA ACU A-3' and 5'-UAG UUC CAA GGU CUG AUA C-3') was prepared. Interestingly enough, siRNA treatment up regulated the luciferase activity which was down regulated by Hoxc8, indicating that Hoxc8 indeed regulates the expression of PCNA, in particular, down regulation in NIN3T3 cells. These results altogether indicate that Hoxc8 might orchestrate the pattern formation by regulating PCNA which is one of the important proteins involved in several processes such as DNA replication and methylation, chromatin remodeling, cell cycle regulation, differentiation, as well as programmed cell death.

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Lentivirus-mediated shRNA Interference Targeting SLUG Inhibits Lung Cancer Growth and Metastasis

  • Wang, Yao-Peng;Wang, Ming-Zhao;Luo, Yi-Ren;Shen, Yi;Wei, Zhao-Xia
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.4947-4951
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    • 2012
  • Objective: Lung cancer is a deadly cancer, whose kills more people worldwide than any other malignancy. SLUG (SNAI2, Snail2) is involved in the epithelial mesenchymal transition in physiological and in pathological contexts and is implicated in the development and progression of lung cancer. Methods: We constructed a lentivirus vector with SLUG shRNA (LV-shSLUG). LV-shSLUG and a control lentivirus were infected into the non-small cell lung cancer cell A549 and real-time PCR, Western blot and IHC were applied to assess expression of the SLUG gene. Cell proliferation and migration were detected using MTT and clony formation methods. Results: Real-time PCR, Western Blot and IHC results confirmed down-regulation of SLUG expression by its shRNA by about 80%~90% at both the mRNA and protein levels. Knockdown of SLUG significantly suppressed lung cancer cell proliferation. Furthermore, knockdown of SLUG significantly inhibited lung cancer cell invasion and metastasis. Finally, knockdown of SLUG induced the down-regulation of Bcl-2 and up-regulation of E-cadherin. Conclusion: These results indicate that SLUG is a newly identified gene associated with lung cancer growth and metastasis. SLUG may serve as a new therapeutic target for the treatment of lung cancer in the future.

Pulegone Exhibits Anti-inflammatory Activities through the Regulation of NF-κB and Nrf-2 Signaling Pathways in LPS-stimulated RAW 264.7 cells

  • Roy, Anupom;Park, Hee-Juhn;Abdul, Qudeer Ahmed;Jung, Hyun Ah;Choi, Jae Sue
    • Natural Product Sciences
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    • v.24 no.1
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    • pp.28-35
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    • 2018
  • Pulegone is a naturally occurring organic compound obtained from essential oils from a variety of plants. The aim of this study was to investigate the anti-inflammatory effects through the inhibitory mechanism of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), nuclear factor kappa B ($NF-{\kappa}B$), mitogen-activated protein kinases (MAPK) pathways and the activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase (HO)-1 pathways in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Results revealed that pulegone significantly inhibited NO production as well as iNOS and COX-2 expressions. Meanwhile, western blot analysis showed that pulegone down-regulated LPS-induced $NF-{\kappa}B$ and MAPKs activation in RAW 264.7 cells. Furthermore, the selected compound suppressed LPS-induced intracellular ROS production in RAW 264.7 cells, while the expression of stress response gene, HO-1, and its transcriptional activator, Nrf-2 was upregulated upon pulegone treatment. Taking together, these findings provided that pulegone inhibited the LPS-induced expression of inflammatory mediators via the down-regulation iNOS, COX-2, $NF-{\kappa}B$, and MAPKs signaling pathways as well as up-regulation of Nrf-2/HO-1 indicating that pulegone has a potential therapeutic and preventive application in various inflammatory diseases.

Intracellular Mg2+ concentration dependent Mg2+ release in the hearts (심장에서 세포내 Mg2+ 농도 의존적 Mg2+ 유리)

  • Baek, Sung-soo;Kim, Shang-jin;Kim, Jln-shang
    • Korean Journal of Veterinary Research
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    • v.40 no.2
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    • pp.291-299
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    • 2000
  • Magnesium ($Mg^{2+}$) transport across the plasma membrane of cardiac myocytes appears to be under hormonal control. Repeated stimulations with adrenergic or histaminergic agonist produced a progressive decrease in $Mg^{2+}$ efflux from hearts. Thus we hypothesized that the $Mg^{2+}$ efflux may be resulted from a down-regulation of receptors or from a depletion of $Mg^{2+}$ from intracellular pool(s) in the hearts. In the present study, the regulation of $Mg^{2+}$ homeostasis by receptor stimulation was studied in perfused rat and guinea pig hearts. The successive short addition of norepinephrine (NE) to rat and guinea pig, and of histamine (HT) to perfused guinea pig hearts induced a progressive decrease in $Mg^{2+}$ efflux. These $Mg^{2+}$ effluxes were blocked by propranolol or ranitidine, respectively. These decrease in $Mg^{2+}$ efflux were inhibited by sodium cyanide (NaCN), which increases intracellular $Mg^{2+}$ ($[Mg^{2+}]_i$) levels. When NE (or HT) was added after HT (or NE), this efflux was also decreased in the guinea pig hearts. In the rat hearts and myocytes, HT did not stimulate $Mg^{2+}$ efflux. But NE produced a large $Mg^{2+}$ efflux after stimulation with HT. 8-(4-Chlorophenylthio)-adenosine cAMP (cAMP), like NE and HT, also induced a progressive decrease in $Mg^{2+}$ efflux in guinea pig hearts. This effect was inhibited by NaCN. These data provide evidence that the progressive decrease in receptor-stimulated $Mg^{2+}$ efflux is considered to be due to a decrease in $[Mg^{2+}]_i$ levels rather than receptor down-regulation.

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