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https://www.readbyqxmd.com/read/28716058/srf-modulates-seizure-occurrence-activity-induced-gene-transcription-and-hippocampal-circuit-reorganization-in-the-mouse-pilocarpine-epilepsy-model
#1
Pascal Lösing, Cristina Elena Niturad, Merle Harrer, Christopher Meyer Zu Reckendorf, Theresa Schatz, Daniela Sinske, Holger Lerche, Snezana Maljevic, Bernd Knöll
A hallmark of temporal lobe epilepsy (TLE) is hippocampal neuronal demise and aberrant mossy fiber sprouting. In addition, unrestrained neuronal activity in TLE patients induces gene expression including immediate early genes (IEGs) such as Fos and Egr1.We employed the mouse pilocarpine model to analyze the transcription factor (TF) serum response factor (SRF) in epileptogenesis, seizure induced histopathology and IEG induction. SRF is a neuronal activity regulated TF stimulating IEG expression as well as nerve fiber growth and guidance...
July 17, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28714032/atf3-promotes-migration-and-m1-m2-polarization-of-macrophages-by-activating-tenascin%C3%A2-c-via-wnt-%C3%AE-%C3%A2-catenin-pathway
#2
Hao Sha, Dianzhong Zhang, Yunfei Zhang, Yanhua Wen, Yucai Wang
There are different polarization states of macrophages, including the classically activated M1 phenotype and the alternatively activated M2 phenotype. These have different functions in the inflammation process. Activating transcription factor 3 (ATF3) is a key transcriptional regulator that inhibits the inflammatory response. However, the effects of ATF3 on migration and anti‑inflammatory control mechanisms of macrophages have not been thoroughly investigated. The present study investigated the effect of ATF3 on macrophage migration and M1/M2 polarization...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28701342/activating-transcription-factor-3-promotes-loss-of-the-acinar-cell-phenotype-in-response-to-cerulein-induced-pancreatitis-in-mice
#3
Elena N Fazio, Claire C Young, Jelena Toma, Michael Levy, Kurt R Berger, Charis L Johnson, Rashid Mehmood, Patrick Swan, Alphonse Chu, Sean P Cregan, F Jeffrey Dilworth, Christopher J Howlett, Christopher L Pin
Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). While down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by Next Generation Sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of more than 30% of differentially expressed genes during the initiation of pancreatitis...
July 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28689354/functional-and-molecular-characterization-of-a-novel-traumatic-peripheral-nerve-muscle-injury-model
#4
Renate Wanner, Manuel Gey, Alireza Abaei, Daniela Warnecke, Luisa de Roy, Lutz Dürselen, Volker Rasche, Bernd Knöll
Traumatic injuries to human peripheral nerves are frequently associated with damage to nerve surrounding tissues including muscles and blood vessels. Currently, most rodent models of peripheral nerve injuries (e.g., facial or sciatic nerve) employ surgical nerve transection with scissors or scalpels. However, such an isolated surgical nerve injury only mildly damages neighboring tissues and weakly activates an immune response. In order to provide a rodent nerve injury model accounting for such nerve-associated tissue damage and immune cell activation, we developed a drop tower-based facial nerve trauma model in mice...
July 8, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28686848/transcriptional-regulation-of-endmt-in-cardiac-fibrosis-role-of-mrtf-a-and-atf3
#5
Vibhuti Sharma, Nilambra Dogra, Uma Saikia, Madhu Khullar
The etiology of cardiac fibrogenesis is quite diverse but a common feature is the presence of activated fibroblasts. Experimental evidence suggests that a subset of cardiac fibroblasts is derived via transition of vascular endothelial cells into fibroblasts by endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their endothelial characteristics and acquire a mesenchymal phenotype. Molecular mechanisms and the transcriptional mediators controlling EndMT in heart during development or disease remain relatively undefined...
July 7, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28684431/convergent-roles-of-atf3-and-csl-in-chromatin-control-of-cancer-associated-fibroblast-activation
#6
Dong Eun Kim, Maria-Giuseppina Procopio, Soumitra Ghosh, Seung-Hee Jo, Sandro Goruppi, Francesco Magliozzi, Pino Bordignon, Victor Neel, Paolo Angelino, G Paolo Dotto
Cancer-associated fibroblasts (CAFs) are important for tumor initiation and promotion. CSL, a transcriptional repressor and Notch mediator, suppresses CAF activation. Like CSL, ATF3, a stress-responsive transcriptional repressor, is down-modulated in skin cancer stromal cells, and Atf3 knockout mice develop aggressive chemically induced skin tumors with enhanced CAF activation. Even at low basal levels, ATF3 converges with CSL in global chromatin control, binding to few genomic sites at a large distance from target genes...
July 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28662411/activating-transcription-factor-3-protects-mice-against-pseudomonas-aeruginosa-induced-acute-lung-injury-by-interacting-with-lipopolysaccharide-binding-protein
#7
Yunfeng Zhao, Xiulin Wu, Lanlan Qian, Liang Guo, Jiangrong Liao, Xueling Wu
Excessive inflammatory response is critical event in the pathogenesis of acute lung injury (ALI). Previous study has shown that activating transcription factor 3 (ATF3) plays a role in downregulate inflammatory responses including ventilation-induced ALI. We hypothesized that ATF3 have a protective effect in ALI induced by pseudomonas aeruginosa. PA was intra-tracheally administrated to ATF3 knock-out (KO) mice to establish ALI model. Inflammatory factors, BALF protein, lung wet to dry ratio, lung injury score and mortality were determined...
June 26, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28662101/specific-gene-expression-signatures-induced-by-the-multiple-oncogenic-alterations-that-occur-within-the-pten-pi3k-akt-pathway-in-lung-cancer
#8
Carmela De Marco, Carmelo Laudanna, Nicola Rinaldo, Duarte Mendes Oliveira, Maria Ravo, Alessandro Weisz, Michele Ceccarelli, Elvira Caira, Antonia Rizzuto, Pietro Zoppoli, Donatella Malanga, Giuseppe Viglietto
Hyperactivation of the phosphatydil-inositol-3' phosphate kinase (PI3K)/AKT pathway is observed in most NSCLCs, promoting proliferation, migration, invasion and resistance to therapy. AKT can be activated through several mechanisms that include loss of the negative regulator PTEN, activating mutations of the catalytic subunit of PI3K (PIK3CA) and/or mutations of AKT1 itself. However, number and identity of downstream targets of activated PI3K/AKT pathway are poorly defined. To identify the genes that are targets of constitutive PI3K/AKT signalling in lung cancer cells, we performed a comparative transcriptomic analysis of human lung epithelial cells (BEAS-2B) expressing active mutant AKT1 (AKT1-E17K), active mutant PIK3CA (PIK3CA-E545K) or that are silenced for PTEN...
2017: PloS One
https://www.readbyqxmd.com/read/28633807/differential-induction-of-atf3-and-ho-1-in-myeloid-cells-and-keratinocytes-via-dimethylfumarate-or-cyclosporine-a
#9
Stefanie Müller, Nikola Smatlik, Marc Burian, Kamran Ghoreschi, Martin Röcken, Amir S Yazdi
BACKGROUND: Chronic inflammatory skin diseases are characterized by controlled proliferation of keratinocytes. Here, activating transcription factor 3 (ATF3) might play a fundamental role. In these inflammatory diseases, proliferation is controlled and only rarely leads to cancer development which can be supported by an inflammatory microenvironment. ATF3 is a dual function protein as it suppresses pro-inflammatory IL-6 and IL-8, but also acts as a pro-oncogenic factor by the suppression of p53...
June 12, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28611196/atf3-repression-of-bcl-xl-determines-apoptotic-sensitivity-tohdac-inhibitors-across-tumour-types
#10
Anderly C Chüeh, Janson Wt Tse, Michael Dickinson, Paul Ioannidis, Laura Jenkins, Lars Tögel, BeeShin Tan, Ian Luk, Mercedes Dávalos-Salas, Rebecca Nightingale, Matthew R Thompson, Bryan Rg Williams, Guillaume Lessene, Erinna F Lee, Walter D Fairlie, Amardeep S Dhillon, John M Mariadason
Purpose: Histone deacetylase inhibitors (HDACi) are epigenome-targeting small molecules approved for the treatment of cutaneous T cell lymphoma and multiple myeloma. They have also demonstrated clinical activity in AML, non-small cell lung cancer and estrogen receptor-positive breast cancer, and trials are underway assessing their activity in combination regimens including immunotherpy.  However, there is currently no clear strategy to reliably predict HDACi sensitivity. <p>In colon cancer cells, apoptotic sensitivity to HDACi is associated with transcriptional induction of multiple immediate-early (IE) genes...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28595284/infertility-diagnosis-has-a-significant-impact-on-the-transcriptome-of-developing-blastocysts
#11
Blair R McCallie, Jason C Parks, Darren K Griffin, William B Schoolcraft, Mandy G Katz-Jaffe
STUDY QUESTION: Is the human blastocyst transcriptome associated with infertility diagnosis, specifically: polycystic ovaries (PCO), male factor (MF), and unexplained (UE)? SUMMARY ANSWER: The global blastocyst transcriptome was significantly altered in association with a PCO, MF, and UE infertility diagnosis. WHAT IS KNOWN ALREADY: Infertility diagnosis has an impact on the probability for a successful outcome following an IVF cycle. Limited information is known regarding the relationship between a specific infertility diagnosis and blastocyst transcription during pre-implantation development...
June 8, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28577574/activating-transcription-factor-3-promotes-embryo-attachment-via-up-regulation-of-leukemia-inhibitory-factor-in-vitro
#12
Xi Cheng, Jingyu Liu, Huizhi Shan, Lihua Sun, Chenyang Huang, Qiang Yan, Ruiwei Jiang, Lijun Ding, Yue Jiang, Jianjun Zhou, Guijun Yan, Haixiang Sun
BACKGROUND: A receptive endometrium is essential for maternal-embryonic molecular communication during implantation. However, the specific molecular regulatory mechanisms of the endometrial capacity remain poorly understood. Here, we examined activating transcription factor 3 (ATF3) expression in human endometria and the functional effect of ATF3 on embryo attachment in vitro. METHODS: Immunohistochemistry (IHC) was used to assess the ATF3 expression patterns in human endometria...
June 2, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28572744/berberine-regulates-the-protein-expression-of-multiple-tumorigenesis-related-genes-in-hepatocellular-carcinoma-cell-lines
#13
Tung-Yueh Chuang, Hsiao-Li Wu, Jie Min, Michael Diamond, Ricardo Azziz, Yen-Hao Chen
BACKGROUND: Hepatocellular carcinoma (HCC) is the seventh most common malignancy and the third leading cause of cancer-related death worldwide with an extremely grim prognosis. Berberine (BBR) has been found to inhibit proliferation of human HCC cells, although the underlying mechanism(s) are unclear. METHODS: Protein expression was detected by Western blots. Cell viability was determined by using the CellTiter Assay kit. RESULTS: We confirm that BBR treatment inhibits HepG2, Hep3B, and SNU-182 cell viability, and suggest that it regulates this proliferation via the modulation of multiple tumorigenesis-related genes protein expression...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28569783/damage-induced-neuronal-endopeptidase-dine-enhances-axonal-regeneration-potential-of-retinal-ganglion-cells-after-optic-nerve-injury
#14
Aoi Kaneko, Sumiko Kiryu-Seo, Sakiko Matsumoto, Hiroshi Kiyama
Damage-induced neuronal endopeptidase (DINE)/endothelin-converting enzyme-like 1 (ECEL1) is a membrane-bound metalloprotease that we identified as a nerve regeneration-associated molecule. The expression of DINE is upregulated in response to nerve injury in both the peripheral and central nervous systems, while its transcription is regulated by the activating transcription factor 3 (ATF3), a potent hub-transcription factor for nerve regeneration. Despite its unique hallmark of injury-induced upregulation, the physiological relevance of DINE in injured neurons has been unclear...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28553505/discovery-of-a-small-molecule-targeting-ulk1-modulated-cell-death-of-triple-negative-breast-cancer-in-vitro-and-in-vivo
#15
Lan Zhang, Leilei Fu, Shouyue Zhang, Jin Zhang, Yuqian Zhao, Yaxin Zheng, Gu He, Shengyong Yang, Liang Ouyang, Bo Liu
UNC-51-like kinase 1 (ULK1) is well-known to initiate autophagy, and the downregulation of ULK1 has been found in most breast cancer tissues. Thus, the activation of ULK1-modulated autophagy could be a promising strategy for breast cancer therapy. In this study, we found that ULK1 was remarkably downregulated in breast cancer tissue samples by The Cancer Genome Atlas (TCGA) analysis and tissue microarray (TMA) analysis, especially in triple negative breast cancer (TNBC). To design a ULK1 agonist, we integrated in silico screening and chemical synthesis to acquire a series of small molecule candidates...
April 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28550532/drug-induced-hsp90-inhibition-alleviates-pain-in-monoarthritic-rats-and-alters-the-expression-of-new-putative-pain-players-at-the-drg
#16
Diana Sofia Marques Nascimento, Catarina Soares Potes, Miguel Luz Soares, António Carlos Ferreira, Marzia Malcangio, José Manuel Castro-Lopes, Fani Lourença Moreira Neto
Purinergic receptors (P2XRs) have been widely associated with pain states mostly due to their involvement in neuron-glia communication. Interestingly, we have previously shown that satellite glial cells (SGC), surrounding dorsal root ganglia (DRG) neurons, become activated and proliferate during monoarthritis (MA) in the rat. Here, we demonstrate that P2X7R expression increases in ipsilateral DRG after 1 week of disease, while P2X3R immunoreactivity decreases. We have also reported a significant induction of the activating transcriptional factor 3 (ATF3) in MA...
May 26, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28549990/early-transcriptome-responses-of-the-bovine-midcycle-corpus-luteum-to-prostaglandin-f2%C3%AE-includes-cytokine-signaling
#17
Heather Talbott, Xiaoying Hou, Fang Qiu, Pan Zhang, Chittibabu Guda, Fang Yu, Robert A Cushman, Jennifer R Wood, Cheng Wang, Andrea S Cupp, John S Davis
In ruminants, prostaglandin F2alpha (PGF2α)-mediated luteolysis is essential prior to estrous cycle resumption, and is a target for improving fertility. To deduce early PGF2α-provoked changes in the corpus luteum a short time-course (0.5-4 h) was performed on cows at midcycle. A microarray-determined transcriptome was established and examined by bioinformatic pathway analysis. Classic PGF2α effects were evident by changes in early response genes (FOS, JUN, ATF3) and prediction of active pathways (PKC, MAPK)...
May 23, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28548885/metformin-inhibits-p-gingivalis-lipopolysaccharide-lps-influenced-inflammatory-response-in-human-gingival-fibroblasts-via-regulating-activating-transcription-factor-3-atf3-expression
#18
Wenyan Kang, Ting Wang, Zhekai Hu, Feng Liu, Yundong Sun, Shaohua Ge
BACKGROUND: Chronic periodontitis is one of the most prevalent oral diseases, which is associated with Porphyromonas gingivalis (P. gingivalis) Lipopolysaccharide (LPS) infection, and has profound effects on type 2 diabetes mellitus (DM2). Metformin, a well-known antidiabetic agent, has been reported to exert anti-inflammatory effects on various cells. This study aimed to investigate the role of metformin on LPS-influenced inflammatory response in human gingival fibroblasts (HGFs). METHODS: Dose-dependent additive effects of metformin on LPS-influenced HGFs were detected...
May 26, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28546922/effect-of-atf3-deletion-on-apoptosis-of-cultured-retinal-ganglion-cells
#19
Ming-Ming Sun, Ya-Chen Wang, Yi Li, Xiao-Dan Guo, Yan-Ming Chen, Zhong-Zhi Zhang
AIM: To investigate the effect of activating transcription factor-3 (ATF3)-deletion on apoptosis of cultured retinal ganglion cells (RGCs). METHODS: Three ATF3 siRNA (ATF3-rat-651, ATF3-rat-319, ATF3-rat-520) were constructed, and were transiently transfected into RGC-5 cells. Quantitative real-time polymerase chain reaction (PCR) was used to examine ATF3 expression and the most effective ATF3 siRNA was selected for further studies. Flow cytometry was applied to investigate the effects of ATF3 deletion on RGC-5 apoptosis under elevated hydrostatic pressure...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28535568/tianeptine-reduces-mechanical-allodynia-in-spinal-nerve-ligated-and-chemotherapy-induced-neuropathic-mice
#20
Seong Min Han, Young Hoon Kim, Hyeon Uk Jo, Jung Ah Kwak, Hue Jung Park
BACKGROUND: Spinal nerve-ligated neuropathy and chemotherapy-induced neuropathy produce a persistent tactile allodynia in mice. Tianeptine is an antidepressant that exhibits structural similarities to tricyclic antidepressants but has distinct neurochemical properties. OBJECTIVE: Here we examined the effects of intraperitoneal (i.p.) tianeptine on allodynia in spinal nerve-ligated and chemotherapy-induced neuropathic mice. STUDY DESIGN: A randomized, experimental trial...
May 2017: Pain Physician
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