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Xiaojuan Xu, Mengmeng Guo, Na Zhang, Shoudong Ye
Although long noncoding RNAs (lncRNAs) are emerging as new modulators in the fate decision of pluripotent stem cells, the functions of specific lncRNAs remain unclear. Here, we found that telomeric RNA (TERRA or TelRNA), one type of lncRNAs, is highly expressed in mouse embryonic stem cells (mESCs), but declines significantly upon differentiation. TERRA is induced by the Wnt/β-catenin signaling pathway and can reproduce its self-renewal-promoting effect when overexpressed. Further studies revealed that TCF3 is a potential downstream target of TERRA and mediates the effect of TERRA in mESC maintenance...
March 7, 2018: American Journal of Physiology. Cell Physiology
Mickael Orgeur, Marvin Martens, Georgeta Leonte, Sonya Nassari, Marie-Ange Bonnin, Stefan T Börno, Bernd Timmermann, Jochen Hecht, Delphine Duprez, Sigmar Stricker
Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling revealed a set of common genes regulated by all five transcription factors, which we propose as connective tissue core expression set...
March 6, 2018: Development
Bendix R Slegtenhorst, Oscar R Fajardo Ramirez, Yuzhi Zhang, Zahra Dhanerawala, Stefan G Tullius, Guillermo García-Cardeña
The vascular endothelium plays a critical role in the health and disease of the cardiovascular system. Importantly, biomechanical stimuli generated by blood flow and sensed by the endothelium constitute important local inputs that are translated into transcriptional programs and functional endothelial phenotypes. Pulsatile, laminar flow, characteristic of regions in the vasculature that are resistant to atherosclerosis, evokes an atheroprotective endothelial phenotype. This atheroprotective phenotype is integrated by the transcription factor Kruppel-like factor-2 (KLF2), and therefore the expression of KLF2 can be used as a proxy for endothelial atheroprotection...
March 1, 2018: SLAS Discovery
N Li, C Liu, D Y Pan, Y Z Tseng, J Zhou, X Q Zeng, T C Luo, S Y Chen
Objective: To investigate the effect and mechanism of Kruppel-like factor 2 (KLF2) on the migration of human liver sinusoidal endothelial cells (LSEC). Methods: Cultured human LSEC were infected with different lenti-viruses to overexpress or suppress KLF2 expression (LV5-KLF2 and LV3-shKLF2, respectively), the infection efficacies were examined by real-time PCR and Western blot analysis.Transwell migration assay was used to investigate the role of KLF2 on the migration of LSEC.The mRNA and protein expression of vascular endothelial growth factor receptor-2 (VEGFR-2) were detected by real-time PCR and Western blot analysis, respectively...
February 13, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Hairong Chu, Hong Li, Xiumei Guan, Hong Yan, Xiaoyun Zhang, Xiaodong Cui, Xin Li, Min Cheng
Cardiovascular risk factors can negatively influence late endothelial progenitor cell (EPCs) number and functions, thus EPCs biology is a clinical implications for cardiovascular diseases. The present study aimed to investigate the potential protective effects of resveratrol (RES) on tumor necrosis factor (TNF)‑α‑induced inflammatory damage in late endothelial progenitor cells (EPCs) and to elucidate the underlying mechanisms. Late EPCs at passages 3‑5 were pretreated with RES at a concentration of 20 µmol/l for 12 h and subsequently incubated with TNF‑α (10 ng/ml) for 24 h...
February 20, 2018: Molecular Medicine Reports
H S Jeffrey Man, Aravin N Sukumar, Gabrielle C Lam, Paul J Turgeon, Matthew S Yan, Kyung Ha Ku, Michelle K Dubinsky, J J David Ho, Jenny Jing Wang, Sunit Das, Nora Mitchell, Peter Oettgen, Michael V Sefton, Philip A Marsden
Endothelial cell (EC)-enriched protein coding genes, such as endothelial nitric oxide synthase (eNOS), define quintessential EC-specific physiologic functions. It is not clear whether long noncoding RNAs (lncRNAs) also define cardiovascular cell type-specific phenotypes, especially in the vascular endothelium. Here, we report the existence of a set of EC-enriched lncRNAs and define a role for s pliced- t ranscript e ndothelial- e nriched lncRNA (STEEL) in angiogenic potential, macrovascular/microvascular identity, and shear stress responsiveness...
February 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
Shaolin He, Chun Wu, Junhui Xiao, Dazhu Li, Ziyan Sun, Ming Li
OBJECTIVE: Endothelial cells (ECs) and macrophages engage in tight and specific interactions that play critical roles in cardiovascular homeostasis and the pathogenesis of atherosclerosis. Extracellular vesicles (EVs) are circular membrane fragments released from the endosomal compartment as exosomes or shed from the surfaces of the membranes of most cell types. Increasing evidence indicates that EVs play a pivotal role in cell-to-cell communication. However, the contribution of EVs, as determine by oxidized low-density lipoprotein (ox-LDL)-exposed and/or Kruppel-like factor 2 (KLF2)-transduced ECs in the interaction between vascular ECs and monocytes/ macrophages, which is a key event in atherosclerotic plaque development, has remained elusive...
February 21, 2018: Scandinavian Journal of Immunology
Feng Li, Jianguang Sun, Shilei Huang, Gao Su, Guofu Pi
BACKGROUND/AIMS: Osteoarthritis (OA) is the most frequently occurring joint disease and characterized by degeneration of cartilage. As the unique cell type in cartilage, chondrocytes play a crucial role during OA. Our study explored the influence of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) on lipopolysaccharides (LPS)-induced injury in ATDC5 cells. METHODS: Cell viability, apoptosis and expression of inflammatory cytokines were all assessed to evaluate LPS-induce inflammatory injury...
February 9, 2018: Cellular Physiology and Biochemistry
Yuehui Wang, Min Sun, Zhe Wang, Xiaonan Li, Yiyi Zhu, Yanhong Li
Oxidation of low-density lipoproteins (ox-LDL) plays a critical role in endothelial dysfunction and the pathological progression of atherosclerosis by causing leukocyte attachment to endothelial surfaces. Omentin-1, an important adipokine primarily secreted by stromal vascular cells, has displayed various biological functions in diverse tissues. However, little information regarding the effects of omentin-1 on ox-LDL- induced endothelial dysfunction has been reported before. In the current study, we found that omentin-1 significantly reduced the attachment of the leukocyte THP-1 cells to human umbilical vein endothelial cells (HUVECs) in a dose dependent manner...
February 2, 2018: Biochemical and Biophysical Research Communications
Ji Yoon Lee, Jihwa Chung, Kyoung Hwa Kim, Shung Hyun An, Minsuk Kim, Junbeom Park, Kihwan Kwon
BACKGROUND AND AIMS: Vascular endothelial cells (ECs) are exposed to fluid shear stress (FSS), which modulates vascular pathophysiology. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is crucial in endothelial dysfunction and atherosclerosis. We elucidated the mechanism regulating LOX-1 expression in ECs by FSS. METHODS: Human umbilical vein endothelial cells were exposed to laminar shear stress (LSS) of indicated intensities using a unidirectional steady flow, or to oscillatory shear stress (OSS) using a bidirectional disturbed flow...
January 31, 2018: Atherosclerosis
Congzhen Qiao, Shengdi Li, Haocheng Lu, Fan Meng, Yanbo Fan, Yanhong Guo, Y Eugene Chen, Jifeng Zhang
Macrophage migration inhibitory factor (MIF) is a non-canonical cytokine that is involved in multiple inflammatory diseases, including atherosclerosis. High MIF expression found in leukocytes which facilitates the initiation and progression of atherosclerosis. However, little is known about biomechanical forces in the induction of MIF in endothelial cells (ECs). Here, we show that laminar shear stress (LS) inhibits the expression of MIF in ECs. By profiling the whole transcriptome of human coronary artery ECs under different shear stress, we found that athero-protective LS attenuates the expression of MIF whereas pro-atherosclerotic oscillatory shear stress (OS) significantly increased the expression of MIF...
February 5, 2018: Scientific Reports
Huipeng Li, Lakshmi Venkatraman, Balakrishnan Chakrapani Narmada, Jacob K White, Hanry Yu, Lisa Tucker-Kellogg
BACKGROUND: Bistable behaviors are prevalent in cell signaling and can be modeled by ordinary differential equations (ODEs) with kinetic parameters. A bistable switch has recently been found to regulate the activation of transforming growth factor-β1 (TGF-β1) in the context of liver fibrosis, and an ordinary differential equation (ODE) model was published showing that the net activation of TGF-β1 depends on the balance between two antagonistic sub-pathways. RESULTS: Through modeling the effects of perturbations that affect both sub-pathways, we revealed that bistability is coupled with the signs of feedback loops in the model...
December 21, 2017: BMC Systems Biology
Keith Saum, Begoña Campos, Diego Celdran-Bonafonte, Lalitha Nayak, Panjamaporn Sangwung, Charuhas Thakar, Prabir Roy-Chaudhury, A Phillip Owens
BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage renal disease. The accumulation of uremic solutes in this patient population is associated with endothelial dysfunction and accelerated cardiovascular disease. In this study, we examined the impact of the uremic milieu on the endothelial transcription factor, Krüppel-like factor 2 (KLF2), a key regulator of endothelial function and activation. METHODS AND RESULTS: Using serum from uremic pigs with chronic renal insufficiency, our results show that KLF2 expression is suppressed by the uremic milieu and individual uremic solutes in vitro...
January 4, 2018: Journal of the American Heart Association
Chiho Koi, Hiroto Izumi, Tomoko Kurita, Thuy Thi Nguyen, Midori Murakami, Yukiko Yoshiura, Toru Hachisuga, Yasuo Morimoto
It was reported that statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase that are used to prevent hypercholesterolemia, have antitumor activity in several cancers. In this study, we investigated the cell viability of statins in Cisplatin-resistant HCP4 and PCDP5 cells compared with their parent Hela and PC3 cells, respectively, and found that HCP4 and PCDP5 cells were 37-fold and 18-fold more resistant to Cisplatin but 13-fold and 7-fold more sensitive to Lovastatin by cell proliferation assay...
December 5, 2017: Oncotarget
Victor Chun-Lam Wong
The gene transactivation function of nuclear EGFR (nEGFR) has been studied by investigating the genomic co-occupancies of nEGFR and RNA Polymerase II (RNAPII). However, due to RNAPII pausing, the co-recruitment of RNAPII and nEGFR does not necessarily represent productive transactivation. In this study, we integrated gatekeepers of productive transcriptional elongation such as Integrator and Super Elongation Complex (SEC) to interrogate the function of nEGFR. By analyzing publicly available ChIP-seq and RNA-seq data, we aims to 1) explore the function of nEGFR, 2) unravel nEGFR target genes, and 3) discuss potential mechanisms of nEGFR chromatin recruitment...
2018: Journal of Cancer
Cody J Wehrkamp, Sathish Kumar Natarajan, Ashley M Mohr, Mary Anne Phillippi, Justin L Mott
MicroRNA dysregulation is a common feature of cancer and due to the promiscuity of microRNA binding this can result in a wide array of genes whose expression is altered. miR-106b is an oncomiR overexpressed in cholangiocarcinoma and its upregulation in this and other cancers often leads to repression of anti-tumorigenic targets. The goal of this study was to identify the miR-106b-regulated gene landscape in cholangiocarcinoma cells using a genome-wide, unbiased mRNA analysis. Through RNA-Seq we found 112 mRNAs significantly repressed by miR-106b...
December 29, 2017: RNA Biology
Xiaobin Li, Zongze Li, Ziwen Liu, Jianchun Xiao, Shuting Yu, Yimin Song
Currently, accumulating documents have paid great attention to the critical role of long non-coding RNAs. The long non-coding RNAs DLEU1 has been demonstrated to be dysregulated in many solid tumors and hematological malignancies. However, the detailed descriptions about its potential roles and molecular mechanism in gastric cancer (GC) are still blurry. As for our research, it was found out that DLEU1 was observably intensified in GC tissues and cell lines. And highly expressed DLEU1 was relevant to tumor size, advanced stage of pathology and lymph node metastasis in GC patients...
December 27, 2017: Cancer Gene Therapy
Chunmei Wang, Liang Li, Qiuhui Duan, Qingqing Wang, Jinlian Chen
Krüppel-like factors (KLFs) are a large family of DNA-binding transcriptional regulators that affect basic cellular processes such as growth, survival, migration and differentiation and serve a complicated function in cancers. KLF2, one member of the KLF family, is dysregulated in many tumors. However, the specific role of KLF2 in human gastric tumorigenesis is unknown. Here we show that the expression of KLF2 protein was lower in gastric tumors when compared with adjacent normal tissue. Moreover, downregulated KLF2 expression in primary gastric tumor was closely correlated with patients' survival...
November 21, 2017: Oncotarget
Mu Liu, Ming Luo, Haoliang Sun, Buqing Ni, Yongfeng Shao
In our aging world, increasing numbers of people are suffering from calcific aortic valve disease (CAVD). In this study, we used integrated bioinformatics analysis to predict several key genes that are involved in the initiation and progression of CAVD. Expression profiles of 15 calcific and 14 normal human aortic valve samples were generated from two gene expression datasets (GSE12644 and GSE51472). Dataset GSE26953 from the human aortic valve fibrosa-derived endothelial cells cultured under laminar or oscillatory shear stress was also evaluated...
December 2017: Tohoku Journal of Experimental Medicine
Yanni Xu, Suowen Xu, Peng Liu, Marina Koroleva, Shuya Zhang, Shuyi Si, Zheng Gen Jin
BACKGROUND: Kruppel-like factor 2 (KLF2) is an important zinc-finger transcription factor that maintains endothelial homeostasis by its anti-inflammatory, -thrombotic, -oxidative, and -proliferative effects in endothelial cells. In light of the potent vasoprotective effects of KLF2, modulating KLF2 expression or function could give rise to new therapeutic strategies to treat cardiovascular diseases. METHODS AND RESULTS: High-throughput drug screening based on KLF2 promoter luciferase reporter assay was performed to screen KLF2 activators...
November 30, 2017: Journal of the American Heart Association
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