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https://www.readbyqxmd.com/read/29322934/computational-analysis-reveals-the-coupling-between-bistability-and-the-sign-of-a-feedback-loop-in-a-tgf-%C3%AE-1-activation-model
#1
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
https://www.readbyqxmd.com/read/29301761/uremic-advanced-glycation-end-products-and-protein-bound-solutes-induce-endothelial-dysfunction-through-suppression-of-kr%C3%A3-ppel-like-factor-2
#2
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
https://www.readbyqxmd.com/read/29290960/lovastatin-induced-kruppel-like-factor-2-klf2-kruppel-like-factor-6-klf6-and-ras-homolog-family-member-b-rhob-genes-and-preferentially-led-to-viability-reduction-of-cisplatin-resistant-cells
#3
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
https://www.readbyqxmd.com/read/29290775/nuclear-egfr-and-integrator-super-elongation-complex-concurrently-binds-to-immediate-early-genes-for-gene-transactivation
#4
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
https://www.readbyqxmd.com/read/29286255/mir-106b-responsive-gene-landscape-identifies-regulation-of-kruppel-like-factor-family
#5
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
https://www.readbyqxmd.com/read/29282356/long-non-coding-rna-dleu1-predicts-poor-prognosis-of-gastric-cancer-and-contributes-to-cell-proliferation-by-epigenetically-suppressing-klf2
#6
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
https://www.readbyqxmd.com/read/29245984/kr%C3%A3-ppel-like-factor-2-suppresses-human-gastric-tumorigenesis-through-inhibiting-pten-akt-signaling
#7
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
https://www.readbyqxmd.com/read/29212967/integrated-bioinformatics-analysis-predicts-the-key-genes-involved-in-aortic-valve-calcification-from-hemodynamic-changes-to-extracellular-remodeling
#8
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...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29191808/suberanilohydroxamic-acid-as-a-pharmacological-kruppel-like-factor-2-activator-that-represses-vascular-inflammation-and-atherosclerosis
#9
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
https://www.readbyqxmd.com/read/29164576/potentiation-of-treatment-efficacy-against-colon-cancer-of-dopamine-via-elevating-klf2-expression-in-tumor-vascular-endothelial-cells
#10
S Chen, Y-M Zhang, Y-G Zhang, J Jia, R-W Zhu
OBJECTIVE: To investigate the anti-tumor effect and potential mechanism of dopamine combined with 5-FU in colon cancer. MATERIALS AND METHODS: Babl/c F1 generation male mice (N = 60) were inoculated with mouse C26 colon cancer cells below the pit to construct colon cancer model. Tumor-bearing mice were then divided into 4 groups (N = 8 each): model control group, dopamine group, 5-FU group and dopamine combined with 5-FU group. Dopamine (100 mg/kg/d) was intraperitoneally injected into mice...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29161413/nrf2-regulates-endothelial-glycolysis-and-proliferation-with-mir-93-and-mediates-the-effects-of-oxidized-phospholipids-on-endothelial-activation
#11
Suvi M Kuosmanen, Emilia Kansanen, Minna U Kaikkonen, Virve Sihvola, Kati Pulkkinen, Henna-Kaisa Jyrkkänen, Pauli Tuoresmäki, Juha Hartikainen, Mikko Hippeläinen, Hannu Kokki, Pasi Tavi, Sami Heikkinen, Anna-Liisa Levonen
Phospholipids, such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC), are the major components of cell membranes. Their exposure to reactive oxygen species creates oxidized phospholipids, which predispose to the development of chronic inflammatory diseases and metabolic disorders through endothelial activation and dysfunction. Although the effects of oxidized PAPC (oxPAPC) on endothelial cells have been previously studied, the underlying molecular mechanisms evoking biological responses remain largely unknown...
November 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29150239/tissue-resident-macrophages-are-locally-programmed-for-silent-clearance-of-apoptotic-cells
#12
Allison W Roberts, Bettina L Lee, Jacques Deguine, Shinu John, Mark J Shlomchik, Gregory M Barton
Although apoptotic cells (ACs) contain nucleic acids that can be recognized by Toll-like receptors (TLRs), engulfment of ACs does not initiate inflammation in healthy organisms. Here we identified macrophage populations that continually engulf ACs in distinct tissues and found that these macrophages share characteristics compatible with immunologically silent clearance of ACs; such characteristics include high expression of AC recognition receptors, low expression of TLR9, and reduced TLR responsiveness to nucleic acids...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29139562/lncrna-ghet1-predicts-poor-prognosis-in-hepatocellular-carcinoma-and-promotes-cell-proliferation-by-silencing-klf2
#13
Li Jin, Yangke He, Shijia Tang, Shan Huang
BACKGROUND: Hepatocellular carcinoma (HCC) has been identified as one of the leading causes of cancer-related death worldwide. Recently, long non-coding RNAs (lncRNAs) attract much attention of researchers, and they are demonstrated to be dysregulated in a variety of cancers, including HCC. LncRNA gastric carcinoma high expressed transcript 1 lncRNA GHET1 is found to be dysregulated in gastric cancer (GC). However, its clinical value and potential biological function in HCC remains unclear...
November 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29137412/long-non-coding-rna-snhg15-inhibits-p15-and-klf2-expression-to-promote-pancreatic-cancer-proliferation-through-ezh2-mediated-h3k27me3
#14
Zhonghua Ma, Hesuyuan Huang, Jirong Wang, Yan Zhou, Fuxing Pu, Qinghong Zhao, Peng Peng, Bingqing Hui, Hao Ji, Keming Wang
Long non-coding RNA (lncRNA) is emerging as an critical regulator in multiple cancers, including pancreatic cancer (PC). Recently, lncRNA SNHG15 was found to be up-regulated in gastric cancer and hepatocellular carcinoma, exerting oncogenic effects. Nevertheless, the biological function and regulatory mechanism of SNHG15 remain unclear in pancreatic cancer (PC). In this study, we reported that SNHG15 expression was also upregulated in PC tissues, and its overexpression was remarkably associated with tumor size, tumor node metastasis (TNM) stage and lymph node metastasis in patients with PC...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29125549/klf2-in-regulation-of-nf-%C3%AE%C2%BAb-mediated-immune-cell-function-and-inflammation
#15
REVIEW
Prerana Jha, Hiranmoy Das
KLF2 (Kruppel-like factor 2) is a member of the zinc finger transcription factor family, which critically regulates embryonic lung development, function of endothelial cells and maintenance of quiescence in T-cells and monocytes. It is expressed in naïve T-cells and monocytes, however its level of expression decreases during activation and differentiation. KLF2 also plays critical regulatory role in various inflammatory diseases and their pathogenesis. Nuclear factor-kappaB (NF-κB) is an important inducer of inflammation and the inflammation is mediated through the transcription of several proinflammatory cytokines, chemokines and adhesion molecules...
November 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29096169/lunasin-abrogates-monocytes-to-endothelial-cells
#16
Yongjun Zhu, Hui Li, Xuezhen Wang
The adherence of monocytes to endothelial cells plays a causal role in the early development of atherosclerosis and is driven by several inflammatory stimuli, which includes oxidized low-density lipoprotein (ox-LDL). Lunasin, a natural peptide identified in soybean seeds, soy-derived food products, other grains and herbal plants, has been found to exert numerous biological activities, including anti-inflammatory and antioxidant properties. However, little is known regarding the mechanism of action of lunasin in ox-LDL-induced endothelial inflammation...
October 30, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29079188/klf2-attenuates-bleomycin-induced-pulmonary-fibrosis-and-inflammation-with-regulation-of-ap-1
#17
Jian Shi, Li-Rong Zhou, Xiao-Sheng Wang, Jun-Feng Du, Ming-Ming Jiang, Zhan Song, Guang-Chao Han, Zhi-Tao Mai
Pulmonary fibrosis (PF) is a chronic, fibrosing interstitial pneumonia and devastating disease. Here we investigated the potential roles of Kruppel-like factor 2 (KLF2) on pulmonary fibrosis and inflammation response. A mouse model of pulmonary fibrosis was established by intratracheal injection of bleomycin (BLM). The mRNA and protein levels of KLF2 were assayed by RT-PCR and Western blotting respectively. The extent of lung fibrosis was determined using hematoxylin and eosin (HE) staining and Masson's trichrome staining, and the hydroxyproline content was quantified...
October 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29056552/hemodynamic-forces-sculpt-developing-heart-valves-through-a-klf2-wnt9b-paracrine-signaling-axis
#18
Lauren M Goddard, Anne-Laure Duchemin, Harini Ramalingan, Bingruo Wu, Mei Chen, Sharika Bamezai, Jisheng Yang, Li Li, Michael P Morley, Tao Wang, Marielle Scherrer-Crosbie, David B Frank, Kurt A Engleka, Stephen C Jameson, Edward E Morrisey, Thomas J Carroll, Bin Zhou, Julien Vermot, Mark L Kahn
Hemodynamic forces play an essential epigenetic role in heart valve development, but how they do so is not known. Here, we show that the shear-responsive transcription factor KLF2 is required in endocardial cells to regulate the mesenchymal cell responses that remodel cardiac cushions to mature valves. Endocardial Klf2 deficiency results in defective valve formation associated with loss of Wnt9b expression and reduced canonical WNT signaling in neighboring mesenchymal cells, a phenotype reproduced by endocardial-specific loss of Wnt9b...
November 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29042072/mir-200b-downregulates-kruppel-like-factor-2-klf2-during-acute-hypoxia-in-human-endothelial-cells
#19
Rafal Bartoszewski, Marcin Serocki, Anna Janaszak-Jasiecka, Sylwia Bartoszewska, Kinga Kochan-Jamrozy, Arkadiusz Piotrowski, Jarosław Króliczewski, James F Collawn
The role of microRNAs in controlling angiogenesis is recognized as a promising therapeutic target in both cancer and cardiovascular disorders. However, understanding a miRNA's pleiotropic effects on angiogenesis is a limiting factor for these types of therapeutic approaches. Using genome-wide next-generation sequencing, we examined the role of an antiangiogenic miRNA, miR-200b, in primary human endothelial cells. The results indicate that miR-200b has complex effects on hypoxia-induced angiogenesis in human endothelia and importantly, that many of the reported miR-200b effects using miRNA overexpression may not be representative of the physiological role of this miRNA...
December 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29023738/klf2-mediates-enhanced-chemoreflex-sensitivity-disordered-breathing-and-autonomic-dysregulation-in-heart-failure
#20
Noah J Marcus, Rodrigo Del Rio, Yanfeng Ding, Harold D Schultz
KEY POINTS: Enhanced carotid body chemoreflex activity contributes to development of disordered breathing patterns, autonomic dysregulation and increases in incidence of arrhythmia in animal models of reduced ejection fraction heart failure. Chronic reductions in carotid artery blood flow are associated with increased carotid body chemoreceptor activity. Krüppel-like Factor 2 (KLF2) is a shear stress-sensitive transcription factor that regulates the expression of enzymes which have previously been shown to play a role in increased chemoreflex sensitivity...
September 6, 2017: Journal of Physiology
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