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Yanxia Wang, Hui Xu, Baoan Zhu, Zhenling Qiu, Zaijun Lin
Background: Tumor microenvironment, in particular the stroma, plays an important role in breast cancer cell invasion and metastasis. Investigation of the molecular characteristics of breast cancer stroma may reveal targets for future study. Methods: The transcriptome profiles of breast cancer stroma and normal breast stroma were compared to identify differentially expressed genes (DEGs). The method was analysis of GSE26910 and GSE10797 datasets. Common DEGs were identified and then analyses of enriched pathways and hub genes were performed...
2018: Cellular & Molecular Biology Letters
Suji Kim, No-Joon Song, Gahee Bahn, Seo-Hyuk Chang, Ui Jeong Yun, Jin-Mo Ku, Dong-Gyu Jo, Kye Won Park
Activating transcription factor 3 (Atf3) has been previously demonstrated to impact obesity and metabolism. However, a metabolic role of Atf3 in mice remains debatable. We investigated the role of Atf3 in mice and further investigated Atf3 expression as a therapeutic target for obesity and metabolic diseases. Atf3 knockout (KO) mice fed with a high fat diet (HFD) aggravated weight gain and impaired glucose metabolism compared to littermate control wild type (WT) mice. Atf3 KO aged mice fed with a chow diet (CD) for longer than 10 months also displayed increased body weight and fat mass compared to WT aged mice...
September 14, 2018: Biochemical and Biophysical Research Communications
Katrin Schaper-Gerhardt, Antje Walter, Christina Schmitz-Rode, Imke Satzger, Ralf Gutzmer
BACKGROUND: Due to their immunosuppressive therapy, organtransplant recipients (OTRs) exhibit a high incidence for the development of cutaneous squamous cell carcinoma (cSCC). Randomized studies of kidney-transplanted patients indicate a significant lower susceptibility for cSCC among patients receiving the mTOR-inhibitor Sirolimus, compared to patients without mTOR-regimen. The exact mechanism, how mTOR inhibition affects keratinocyte carcinogenesis remains unclear. OBJECTIVE: Our aim was to investigate the impact of Sirolimus on the expression level of the oncogene ATF3, which is involved in the development and progression of cSCC...
September 5, 2018: Journal of Dermatological Science
Seungyeop Lee, Gyu-Lee Kim, Na Young Kim, Se-Jin Kim, Prachetash Ghosh, Dong-Kwon Rhee
Activating transcription factor-3 (ATF3) in the ER stress pathway induces cytokine production and promotes survival during gram-positive bacterial infection. IL-17A is a critical cytokine that is essential for clearance of Streptococcus pneumoniae . However, the mechanism by which ATF3 induces IL-17A production remains unknown. Here, we show that ATF3 induces IL-17A production via NLRP3 inflammasome-dependent IL-1β secretion. Survival rates were comparable in IL-17A-depleted and ATF3 KO mice but were lower than in WT mice treated with isotype control, indicating that ATF3 positively regulated IL-17A production...
2018: Frontiers in Immunology
Melissa S O'Brien, Holly T A Philpott, Jason J McDougall
Joint neuropathic pain occurs in a subset of arthritis patients and lysophosphatidic acid (LPA) has been implicated as a mediator of joint neuropathy. The mechanism by which LPA promotes neuropathic pain is unknown but may be related to altered signalling of the voltage-gated sodium channel NaV1.8 located on nociceptors. Since arthritis and neuropathic pain are more prevalent in women, this study aimed to explore potential sex-differences in the development of LPA-induced joint neuropathy and whether NaV1.8 played a role in the associated neuropathic pain...
September 11, 2018: Pain
Zhaoyan Li, Qingyu Wang, Gaoyang Chen, Xin Li, Qiwei Yang, Zhenwu Du, Ming Ren, Yang Song, Guizhen Zhang
Osteoarthritis (OA) is one of the most common diseases worldwide, but the pathogenic genes and pathways are largely unclear. The aim of this study was to screen and verify hub genes involved in OA and explore potential molecular mechanisms. The expression profiles of GSE12021 and GSE55235 were downloaded from the Gene Expression Omnibus (GEO) database, which contained 39 samples, including 20 osteoarthritis synovial membranes and 19 matched normal synovial membranes. The raw data were integrated to obtain differentially expressed genes (DEGs) and were deeply analyzed by bioinformatics methods...
2018: BioMed Research International
Qiang Zhu, Han Wang, Bin Jiang, Xuhao Ni, Longfeng Jiang, Changyong Li, Xuehao Wang, Feng Zhang, Bibo Ke, Ling Lu
Activating transcription factor 3 (ATF3) is a stress-induced transcription factor that plays important roles in regulating immune and metabolic homeostasis. Activation of the mechanistic target of rapamycin (mTOR) and hypoxia-inducible factor (HIF) transcription factors are crucial for the regulation of immune cell function. Here, we investigated the mechanism by which the ATF3/mTOR/HIF-1 axis regulates immune responses in a liver ischemia/reperfusion injury (IRI) model. Deletion of ATF3 exacerbated liver damage, as evidenced by increased levels of serum ALT, intrahepatic macrophage/neutrophil trafficking, hepatocellular apoptosis, and the upregulation of pro-inflammatory mediators...
September 5, 2018: Cell Death & Disease
Robert J Danaher, Liping Zhang, Connor J Donley, Nashwin A Laungani, S Elise Hui, Craig S Miller, Karin N Westlund
Chronic orofacial pain is a significant health problem requiring identification of regulating processes. Involvement of epigenetic modifications that is reported for hindlimb neuropathic pain experimental models, however, is less well studied in cranial nerve pain models. Three independent observations reported here are the (1) epigenetic profile in mouse trigeminal ganglia (TG) after trigeminal inflammatory compression (TIC) nerve injury mouse model determined by gene expression microarray, (2) H3K9 acetylation pattern in TG by immunohistochemistry, and (3) efficacy of histone deacetylase (HDAC) inhibitors to attenuate development of hypersensitivity...
January 2018: Molecular Pain
M Rohini, A Haritha Menon, N Selvamurugan
Activating transcription factor 3 (ATF3) is a stress-responsive factor that belongs to the activator protein 1 (AP-1) family of transcription factors. ATF3 expression is stimulated by various factors such as hypoxia, cytokines, and chemotherapeutic and DNA damaging agents. Upon stimulation, ATF3 can form homodimers or heterodimers with other members of the AP-1 family to repress or activate transcription. Under physiological conditions, ATF3 expression is transient and plays a pivotal role in controlling the expression of cell-cycle regulators and tumor suppressor, DNA repair, and apoptosis genes...
August 23, 2018: International Journal of Biological Macromolecules
Suji Kim, No-Joon Song, Seo-Hyuk Chang, Gahee Bahn, Yuri Choi, Dong-Kwon Rhee, Ui Jeong Yun, Jinhee Choi, Jeon Lee, Jae Hyuk Yoo, Donghan Shin, Ki-Moon Park, Hee Kang, Sukchan Lee, Jin-Mo Ku, Yoon Shin Cho, Kye Won Park
The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT...
August 22, 2018: Biomolecules & Therapeutics
Deborah M Hegarty, Sam M Hermes, Michael M Morgan, Sue A Aicher
Introduction: Corneal nerves mediate pain from the ocular surface, lacrimation, and blinking, all of which protect corneal surface homeostasis and help preserve vision. Because pain, lacrimation and blinking are rarely assessed at the same time, it is not known whether these responses and their underlying mechanisms have similar temporal dynamics after acute corneal injury. Methods: We examined changes in corneal nerve density, evoked and spontaneous pain, and ocular homeostasis in Sprague-Dawley male rats after a superficial epithelial injury with heptanol...
July 2018: Pain Reports (Baltimore, Md.)
Wenyan Zhao, Ming Sun, Shuqiang Li, Zhaofu Chen, Donghua Geng
This study was designed to research the influence of activating transcription factor 3 (ATF3) on the radioresistance of breast cancer. ATF3 expression was measured by qRT-PCR and immunohistochemistry. Cancerous cell lines were cultured in vitro, and the expression of ATF3 was gauged by both qRT-PCR and Western blot before and after the radiation therapy. Cellular cycle and apoptosis were analysed by flow cytometry. Changes in the expression of corresponding proteins in the downstream pathways were identified by Western blot...
August 17, 2018: Journal of Cellular and Molecular Medicine
Heng Zhou, Ning Li, Yuan Yuan, Ya-Ge Jin, Haipeng Guo, Wei Deng, Qi-Zhu Tang
Cardiovascular diseases (CVDs) are the primary causes of death worldwide. Among the numerous signaling molecules involved in CVDs, transcriptional factors directly influence gene expression and play a critical role in regulating cell function and the development of diseases. Activating transcription factor (ATF) 3 is an adaptive-response gene in the ATF/cAMP responsive element-binding (CREB) protein family of transcription factors that acts as either a repressor or an activator of transcription via the formation of homodimers or heterodimers with other ATF/CREB members...
August 9, 2018: Basic Research in Cardiology
Matt C Danzi, Saloni T Mehta, Kireeti Dulla, Giulia Zunino, Daniel J Cooper, John L Bixby, Vance P Lemmon
Axon regeneration is a necessary step toward functional recovery after spinal cord injury. The AP-1 transcription factor c-Jun has long been known to play an important role in directing the transcriptional response of Dorsal Root Ganglion (DRG) neurons to peripheral axotomy that results in successful axon regeneration. Here we performed ChIPseq for Jun in mouse DRG neurons after a sciatic nerve crush or sham surgery in order to measure the changes in Jun's DNA binding in response to peripheral axotomy. We found that the majority of Jun's injury-responsive changes in DNA binding occur at putative enhancer elements, rather than proximal to transcription start sites...
August 3, 2018: Molecular and Cellular Neurosciences
M Rohini, M Gokulnath, P J Miranda, N Selvamurugan
We previously reported that ATF3 and Runx2 are involved in breast cancer progression and bone metastasis. The expression of these genes can be controlled by post-transcriptional regulators such as microRNAs (miRNAs). In this study, we identified and validated the functional role of miR-590-3p in human breast cancer cells (MDA-MB231). There was an inverse correlation between the expression of miR-590-3p and its putative target genes, ATF3 and Runx2 in these cells. Overexpression of miR-590-3p decreased the expression of ATF3 and Runx2 at the mRNA and protein levels in MDA-MB231 cells...
August 1, 2018: Biochimie
Austin I McDonald, Aditya S Shirali, Raquel Aragón, Feiyang Ma, Gloria Hernandez, Don A Vaughn, Julia J Mack, Tiffany Y Lim, Hannah Sunshine, Peng Zhao, Vladimir Kalinichenko, Tsonwin Hai, Matteo Pelegrini, Reza Ardehali, M Luisa Iruela-Arispe
The cellular and mechanistic bases underlying endothelial regeneration of adult large vessels have proven challenging to study. Using a reproducible in vivo aortic endothelial injury model, we characterized cellular dynamics underlying the regenerative process through a combination of multi-color lineage tracing, parabiosis, and single-cell transcriptomics. We found that regeneration is a biphasic process driven by distinct populations arising from differentiated endothelial cells. The majority of cells immediately adjacent to the injury site re-enter the cell cycle during the initial damage response, with a second phase driven by a highly proliferative subpopulation...
August 2, 2018: Cell Stem Cell
Fumihiro Shiromoto, Hussein H Aly, Haruka Kudo, Koichi Watashi, Asako Murayama, Noriyuki Watanabe, Xin Zheng, Takanobu Kato, Kazuaki Chayama, Masamichi Muramatsu, Takaji Wakita
Hepatitis B virus (HBV) -x protein is a transcriptional regulator required for the HBV life cycle. HBx also induces complications in the host such as hepatocellular carcinoma. We previously showed that HBx mRNA is degraded by the Ski2/RNA exosome complex. In the present study, we report the regulation of this system through the control of Ski2 expression. We identified interleukin (IL) -1β as an inducer of expression from the Ski2 promoter. IL-1β induced the expression of ATF3 transcription factor, which in turn binds to cyclic AMP-responsive element sequence in the Ski2 promoter and is responsible for Ski2 promoter induction by IL-1β...
September 10, 2018: Biochemical and Biophysical Research Communications
Kumar Abhishek, Sushmita Das, Ashish Kumar, Ajay Kumar, Vinod Kumar, Savita Saini, Abhishek Mandal, Sudha Verma, Manjay Kumar, Pradeep Das
BACKGROUND: Endoplasmic reticulum (ER) stress generated unfolded stress response (UPR) is a basic survival mechanism which protects cell under unfavourable conditions. Leishmania parasite modulates host macrophages in various ways to ensure its survival. Modulation of PI3K-Akt pathway in delayed apoptotic induction of host; enables parasite to stabilize the infection for further propagation. METHODOLOGY: Infected RAW macrophages were exposed to campothecin or thagsigargin and phosphorylation status of PERK, Akt, BAD and Cyt-C was determined through western blotting using phospho specific antibody...
July 2018: PLoS Neglected Tropical Diseases
Josiane Érica Miyamoto, Ana Carolina G Ferraz, Mariana Portovedo, Andressa Reginato, Marcella Aparecida Stahl, Leticia Martins Ignacio-Souza, Kenny L Chan, Adriana Souza Torsoni, Marcio Alberto Torsoni, Ana Paula Badan Ribeiro, Marciane Milanski
Interesterified fats have largely replaced hydrogenated vegetable fat, which is rich in trans fatty acids, in the food industry as an economically viable alternative, generating interest to study their health effects. The aim of this study was to evaluate the effect that interesterification of oils and fat has on lipid-induced metabolic dysfunction, hepatic inflammation and ER stress. Five week-old male Wistar rats were randomly divided into three experimental groups, submitted to either normocaloric and normolipidic diet containing 10% of lipids from unmodified soybean oil (SO) or from interesterified soybean oil (ISO), and one more group submitted to a high fat diet (HFD) containing 60% of fat from lard as a positive control, for 8 or 16 weeks...
September 2018: Journal of Nutritional Biochemistry
David I Bernstein, Zana L Lummus, Banu Kesavalu, Jianbo Yao, Leah Kottyan, Daniel Miller, André Cartier, Maria-Jesús Cruz, Catherine Lemiere, Xavier Muñoz, Santiago Quirce, Susan Tarlo, Joaquin Sastre, Louis Philippe Boulet, Matthew T Weirauch, Kenneth Kaufman
BACKGROUND: Isocyanates are major causes of occupational asthma, but susceptibility and mechanisms of diisocyanate-induced asthma (DA) remain uncertain. OBJECTIVE: The aim of this study was to identify DA-associated functional genetic variants through next-generation sequencing (NGS), bioinformatics, and functional assays. METHODS: NGS was performed in 91 workers with DA. Fourteen loci with known DA-associated single nucleotide polymorphisms (SNPs) were sequenced and compared with data from 238 unexposed subjects...
September 2018: Journal of Allergy and Clinical Immunology
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