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Hypoxia-inducible Factor-2α-dependent Hypoxic Induction of Wnt10b Expression in Adipogenic Cells
Park, Young-Kwon,Park, Bongju,Lee, Seongyeol,Choi, Kang,Moon, Yunwon,Park, Hyunsung American Society for Biochemistry and Molecular Bi 2013 The Journal of biological chemistry Vol.288 No.36
<P>Adipocyte hyperplasia and hypertrophy in obesity can lead to many changes in adipose tissue, such as hypoxia, metabolic dysregulation, and enhanced secretion of cytokines. In this study, hypoxia increased the expression of Wnt10b in both human and mouse adipogenic cells, but not in hypoxia-inducible factor (HIF)-2α-deficient adipogenic cells. Chromatin immunoprecipitation analysis revealed that HIF-2α, but not HIF-1α, bound to the <I>Wnt10b</I> enhancer region as well as upstream of the <I>Wnt1</I> gene, which is encoded by an antisense strand of the <I>Wnt10b</I> gene. Hypoxia-conditioned medium (H-CM) induced phosphorylation of lipoprotein-receptor-related protein 6 as well as β-catenin-dependent gene expression in normoxic cells, which suggests that H-CM contains canonical Wnt signals. Furthermore, adipogenesis of both human mesenchymal stem cells and mouse preadipocytes was inhibited by H-CM even under normoxic conditions. These results suggest that O<SUB>2</SUB> concentration gradients influence the formation of Wnt ligand gradients, which are involved in the regulation of pluripotency, cell proliferation, and cell differentiation.</P>
( Sehhoon Park ),( Seongyeol Park ),( Se-hoon Lee ),( Beomseok Suh ),( Bhumsuk Keam ),( Tae Min Kim ),( Dong-wan Kim ),( Young Whan Kim ),( Dae Seog Heo ) 대한내과학회 2016 The Korean Journal of Internal Medicine Vol.31 No.6
Background/Aims: Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. Methods: A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. Results: In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p < 0.001) were poor prognostic factors for PFS. Among them, BMI and PNI were independent in multi-variable analysis. All of these were also significant prognostic values for OS. The higher the sum of scores, the poorer PFS and OS were observed. Conclusions: Pretreatment nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.
Multi-dimensional histone methylations for coordinated regulation of gene expression under hypoxia
Lee, Seongyeol,Lee, Jieon,Chae, Sehyun,Moon, Yunwon,Lee, Ho-Youl,Park, Bongju,Yang, Eun Gyeong,Hwang, Daehee,Park, Hyunsung Oxford University Press 2017 Nucleic acids research Vol.45 No.20
<P><B>Abstract</B></P><P>Hypoxia increases both active and repressive histone methylation levels via decreased activity of histone demethylases. However, how such increases coordinately regulate induction or repression of hypoxia-responsive genes is largely unknown. Here, we profiled active and repressive histone tri-methylations (H3K4me3, H3K9me3, and H3K27me3) and analyzed gene expression profiles in human adipocyte-derived stem cells under hypoxia. We identified differentially expressed genes (DEGs) and differentially methylated genes (DMGs) by hypoxia and clustered the DEGs and DMGs into four major groups. We found that each group of DEGs was predominantly associated with alterations in only one type among the three histone tri-methylations. Moreover, the four groups of DEGs were associated with different TFs and localization patterns of their predominant types of H3K4me3, H3K9me3 and H3K27me3. Our results suggest that the association of altered gene expression with prominent single-type histone tri-methylations characterized by different localization patterns and with different sets of TFs contributes to regulation of particular sets of genes, which can serve as a model for coordinated epigenetic regulation of gene expression under hypoxia.</P>
Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma
Lee, Jake June-Koo,Park, Seongyeol,Park, Hansol,Kim, Sehui,Lee, Jongkeun,Lee, Junehawk,Youk, Jeonghwan,Yi, Kijong,An, Yohan,Park, In Kyu,Kang, Chang Hyun,Chung, Doo Hyun,Kim, Tae Min,Jeon, Yoon Kyung Elsevier 2019 Cell Vol.177 No.7
Ko, Seongyeol,Gu, Min Jeong,Kim, Cheol Gyun,Kye, Yoon Chul,Lim, Younggap,Lee, Ji Eun,Park, Byung-Chul,Chu, Hyuk,Han, Seung Hyun,Yun, Cheol-Heui ELSEVIER 2017 ANTIVIRAL RESEARCH Vol.146 No.-
<P>Porcine epidemic diarrhea virus (PEDV) invades porcine intestinal epithelial cells (IECs) and causes diarrhea and dehydration in pigs. In the present study, we showed a suppression of PEDV infection in porcine jejunum intestinal epithelial cells (IPEC-J2) by an increase in autophagy. Autophagy was activated by rapamycin at a dose that does not affect cell viability and tight junction permeability. The induction of autophagy was examined by LC3I/LC3II conversion. To confirm the autophagic-flux (entire autophagy pathway), autophagolysosomes were examined by an immunofluorescence assay. Pretreatment with rapamycin significantly restricted not only a 1 h infection but also a longer infection (24 h) with PEDV, while this effect disappeared when autophagy was blocked. Co-localization of PEDV and autophagosomes suggests that PEDV could be a target of autophagy. Moreover, alleviation of PEDV-induced cell death in IPEC-J2 cells pretreated with rapamycin demonstrates a protective effect of rapamycin against PEDV-induced epithelial cell death. Collectively, the present study suggests an early prevention against PEDV infection in IPEC-J2 cells via autophagy that might be an effective strategy for the restriction of PEDV, and opens up the possibility of the use of rapamycin in vivo as an effective prophylactic and prevention treatment. (C) 2017 Elsevier B.V. All rights reserved.</P>