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Jidong Chen, Xiaolei Cui, Zhengjiang Qian, Yanjiao Li, Kang Kang, Junle Qu, Li Li, Deming Gou
BACKGROUND: Pulmonary arterial hypertension (PAH) is a lethal disease with pronounced narrowing of pulmonary vessels due to abnormal cell proliferation. The platelet-derived growth factor BB (PDGF-BB) is well known as a potent mitogen for smooth muscle cell proliferation. To better understand how this growth factor regulates pulmonary arterial smooth muscle cells (PASMCs) proliferation, we sought to characterize the response to PDGF-BB stimulation at system-wide levels, including the transcriptome and proteome...
October 6, 2016: BMC Genomics
Christophe Louis Depoix, Olivier Flabat, Frédéric Debiève, Corinne Hubinont
During the first trimester of pregnancy, placenta formation probably occurs in a low-oxygen environment necessary to protect cytotrophoblasts from oxidative stress and to allow proper gene regulation. Transcription factors involved in gene regulation under low oxygen tension are the hypoxia-inducible factors, mainly HIF1A, EPAS1 and their dimerization partner HIF1B. Little is known about their expression during in vitro culture of cytotrophoblasts under chronic hypoxia. We assessed HIF1A and EPAS1 expression in a 4-day in vitro culture of primary term cytotrophoblasts under 21% O2 and 2...
September 2016: Reproductive Biology
F X Donadeu, B T Mohammed, J Ioannidis
In a previous microarray study, we identified a subset of micro RNAS (miRNAs), which expression was distinctly higher in atretic than healthy follicles of cattle. In the present study, we investigated the involvement of those miRNAs in granulosa and theca cells during atresia. Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) confirmed that miR-21-5p/-3p, miR-150, miR-409a, miR-142-5p, miR-378, miR-222, miR-155, and miR-199a-5p were expressed at higher levels in atretic than healthy follicles (9-17 mm, classified based on steroidogenic capacity)...
August 13, 2016: Domestic Animal Endocrinology
Lucija Slemc, Tanja Kunej
Hypoxia-inducible factor-1α (HIF-1α) has crucial role in adapting cells to hypoxia through expression regulation of many genes. Identification of HIF-1α target genes (HIF-1α-TGs) is important for understanding the adapting mechanism. The aim of the present study was to collect known HIF-1α-TGs and identify their associated pathways. Targets and associated genomics data were retrieved using PubMed, WoS ( ), HGNC ( ), NCBI ( http://www.ncbi.nlm.nih...
September 19, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Ines Soro-Arnaiz, Qilong Oscar Yang Li, Mar Torres-Capelli, Florinda Meléndez-Rodríguez, Sónia Veiga, Koen Veys, David Sebastian, Ainara Elorza, Daniel Tello, Pablo Hernansanz-Agustín, Sara Cogliati, Jose Maria Moreno-Navarrete, Eduardo Balsa, Esther Fuertes, Eduardo Romanos, Antonio Martínez-Ruiz, Jose Antonio Enriquez, Jose Manuel Fernandez-Real, Antonio Zorzano, Katrien De Bock, Julián Aragonés
Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation...
September 13, 2016: Cell Reports
Chidiebere U Awah, Stephanie Tamm, Silke Hedtfeld, Doris Steinemann, Burkhard Tümmler, Georgios Tsiavaliaris, Frauke Stanke
A challenging question in genetics is to understand the molecular function of non-coding variants of the genome. By using differential EMSA, ChIP and functional genome analysis, we have found that changes in transcription factors (TF) apparent binding affinity and dissociation rates are responsible for allele specific assembly or disruption of master TFs: we observed that NF-KBp50, NF-KBp65 and HIF1a bind with an affinity of up to 10 fold better to the C-allele than to the T-allele of rs7901656 both in vivo and in vitro...
September 9, 2016: Biochimica et Biophysica Acta
Guodong Han, Shu Zhang, Yunwei Dong
Organisms on the rocky shore frequently suffer from high temperature, which consequently causes disability of cardiac function and retards the cellular oxygen delivery. However, some gastropods can survive in several Celsius degrees higher than their Arrhenius break temperature of cardiac function (ABT), indicating the importance of anaerobic metabolism for their thermal tolerance. We measured the global molecular responses to heat stress in limpet Cellana toreuma using 454 GS-FLX to investigate the variations of genes involving in anaerobic metabolism at high temperature...
September 5, 2016: Integrative Zoology
Aneta A Koronowicz, Paula Banks, Dominik Domagała, Adam Master, Teresa Leszczyńska, Ewelina Piasna, Mariola Marynowska, Piotr Laidler
BACKGROUND: Our previous study showed that fatty acids extract obtained from CLA-enriched egg yolks (EFA-CLA) suppressed the viability of MCF-7 cancer cell line more effectively than extract from non-enriched egg yolks (EFA). In this study, we analysed the effect of EFA-CLA and EFA on transcriptome profile of MCF-7 cells by applying the whole Human Genome Microarray technology. RESULTS: We found that EFA-CLA and EFA treated cells differentially regulated genes involved in cancer development and progression...
2016: Genes & Nutrition
Matija Hedl, Jie Yan, Clara Abraham
Interferon regulatory factor 5 (IRF5) regulates inflammatory M1 macrophage polarization, and disease-associated IRF5 genetic variants regulate pattern-recognition-receptor (PRR)-induced cytokines. PRR-stimulated macrophages and M1 macrophages exhibit enhanced glycolysis, a central mediator of inflammation. We find that IRF5 is needed for PRR-enhanced glycolysis in human macrophages and in mice in vivo. Upon stimulation of the PRR nucleotide binding oligomerization domain containing 2 (NOD2) in human macrophages, IRF5 binds RIP2, IRAK1, and TRAF6...
August 30, 2016: Cell Reports
Gülen Yerlikaya, Sukirthini Balendran, Katharina Pröstling, Theresa Reischer, Peter Birner, Rene Wenzl, Lorenz Kuessel, Berthold Streubel, Heinrich Husslein
OBJECTIVE: Endometriosis is a benign gynaecological disease, affecting women during their reproductive years. Angiogenesis represents a crucial step in the pathogenesis of endometriosis, because endometriotic lesions require neovascularization. In this study several angiogenesis-related genes have been studied in the context of endometriosis. Some of the analyzed angiogenic factors as well as their interactions were studied the first time regarding a possible association with endometriosis...
September 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
Stefan Stremitzer, Wu Zhang, Dongyun Yang, Yan Ning, Yu Sunakawa, Satoshi Matsusaka, Anish Parekh, Satoshi Okazaki, Diana Hanna, Stephanie H Astrow, Miriana Moran, Jose Hernandez, Craig Stephens, Stefan J Scherer, Judith Stift, Friedrich Wrba, Thomas Gruenberger, Heinz-Josef Lenz
Angiogenesis-related gene expression is associated with the efficacy of anti-VEGF therapy. We tested whether intratumoral mRNA expression levels of genes involved in vascular morphogenesis and early vessel maturation predict response, recurrence-free survival (RFS), and overall survival (OS) in a unique cohort of patients with colorectal liver metastases (CLM) treated with bevacizumab-based chemotherapy followed by curative liver resection. Intratumoral mRNA was isolated from resected bevacizumab-pretreated CLM from 125 patients...
August 17, 2016: Molecular Cancer Therapeutics
Désirée Schönenberger, Michal Rajski, Sabine Harlander, Ian J Frew
One of the earliest requirements for the formation of a solid tumor is the establishment of an adequate blood supply. Clear cell renal cell carcinomas (ccRCC) are highly vascularized tumors in which the earliest genetic event is most commonly the biallelic inactivation of the VHL tumor suppressor gene, leading to constitutive activation of the HIF-1α and HIF-2α transcription factors, which are known angiogenic factors. However it remains unclear whether either or both HIF-1α or HIF-2α stabilization in normal renal epithelial cells are necessary or sufficient for alterations in blood vessel formation...
August 12, 2016: Oncotarget
Yuan Yao, Qiyue Deng, Weilin Song, Huiyu Zhang, Yuanjing Li, Yang Yang, Xin Fan, Minghan Liu, Jin Shang, Chao Sun, Yu Tang, Xiangting Jin, Huan Liu, Bo Huang, Yue Zhou
Degenerative cartilage endplate (CEP) shows decreased chondrification and increased ossification. Cartilage endplate stem cells (CESCs), with the capacity for chondro-osteogenic differentiation, are responsible for CEP restoration. CEP is avascular and hypoxic, while the physiological hypoxia is disrupted in the degenerated CEP. Hypoxia promoted chondrogenesis but inhibited osteogenesis in CESCs. This tissue-specific differentiation fate of CESCs in response to hypoxia was physiologically significant with regard to CEP maintaining chondrification and refusing ossification...
August 9, 2016: Stem Cell Reports
Joan J Castellano, Alfons Navarro, Nuria Viñolas, Ramon M Marrades, Jorge Moises, Anna Cordeiro, Adela Saco, Carmen Muñoz, Dolors Fuster, Laureano Molins, Josep Ramirez, Mariano Monzo
INTRODUCTION: Long intergenic noncoding RNA-p21 (lincRNA-p21) is a long noncoding RNA transcriptionally activated by tumor protein p53 (TP53) and hypoxia inducible factor 1 alpha subunit (HIF1A). It is involved in the regulation of TP53-dependent apoptosis and the Warburg effect. We have investigated the role of lincRNA-p21 in NSCLC. METHODS: LincRNA-p21 expression was assessed in tumor and normal tissue from 128 patients with NSCLC and correlated with time to relapse and cancer-specific survival (CSS)...
August 2, 2016: Journal of Thoracic Oncology
Aarti Sethuraman, Martin Brown, Tiffany N Seagroves, Zhao-Hui Wu, Lawrence M Pfeffer, Meiyun Fan
BACKGROUND: While aberrant activation of the chromatin-remodeling SWI/SNF complexes has been associated with cancer development and progression, the role of each subunit in tumor cells is poorly defined. This study is aimed to characterize the role of SMARCE1/BAF57 in regulating metastasis of breast cancer cells. METHODS: Genetic approaches and chemical inhibitors were used to manipulate the activities of SMARCE1 and its downstream targets in multiple breast cancer cell lines...
2016: Breast Cancer Research: BCR
Haley R Noonan, Ana M Metelo, Caramai N Kamei, Randall T Peterson, Iain A Drummond, Othon Iliopoulos
Patients with von Hippel-Lindau (VHL) disease harbor a germline mutation in the VHL gene leading to the development of several tumor types including clear cell renal cell carcinoma (ccRCC). In addition, the VHL gene is inactivated in over 90% of sporadic ccRCC cases. 'Clear cell' tumors contain large, proliferating cells with 'clear cytoplasm', and a reduced number of cilia. VHL inactivation leads to the stabilization of hypoxia inducible factors 1a and 2a [HIF1a and HIF2a (HIF2a is also known as EPAS1)] with consequent up-regulation of specific target genes involved in cell proliferation, angiogenesis and erythropoiesis...
August 1, 2016: Disease Models & Mechanisms
Alice Nomura, Patricia Dauer, Vineet Gupta, Olivia McGinn, Nivedita Arora, Kaustav Majumdar, Charles Uhlrich Iii, Joseph Dalluge, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Chemoresistance in pancreatic cancer has been attributed to tumor-initiating cells (TICs), a minor sub-population of tumor cells. However, the mechanism of chemo-resistance in these cells is still unclear.In the current study, immunohistochemical analysis of LSL-KrasG12D; LSL-Trp53R172H;PdxCre (KPC) murine tumors indicated that hypoxic regions developed through tumor progression. This hypoxic "niche" correlated with increased CD133+ population that had an increased HIF1A activity. Consistent with this observation, CD133+ cells had increased glucose uptake and activity of glycolytic pathway enzymes compared to CD133- cells...
July 26, 2016: Oncotarget
Lili Du, Liyun Kuang, Wenting Tang, Dunjin Chen
OBJECTIVE: To study the effects of decabrominated biphenyl ether (BDE-209) exposure on differentiation capacity of human embryonic stem cells. METHODS: Human embryonic stem cell line FY-hES-10 cells were exposed to the concentrations of 0 (solvent control), 1, 10 to 100 nmol/L BDE-209 for 96 h and then were differentiated into embryoid bodies (EBs) in vitro. The RNA of EBs derived from FY-hES-10 cells at Day 10 was collected. OCT4,three-layer differentiation-related genes (AFP,SMA and PAX6) and oxidative stress-related genes (HIF1a, HIF2a and SOD1) expression was detected by Q-PCR...
May 2016: Wei Sheng Yan Jiu, Journal of Hygiene Research
Natalia Garay-Lugo, Aarón Domínguez-Lopez, Angel Miliar García, Eliud Aguilar Barrera, Modesto Gómez López, Alejandro Gómez Alcalá, Maria de Los Angeles Martínez Godinez, Eleazar Lara-Padilla
CONTEXT: There is evidence that n-3 polyunsaturated fatty acids (n-3-PUFAs) can inhibit mTORC1, which should potentiate autophagy and eliminate NLRP3 inflammasome activity. OBJECTIVE: Evaluate the effect of a high-fat or high-fat/fructose diet with and without n-3-PUFAs on hepatic gene expression. MATERIALS AND METHODS: We examined the mRNA expression by RT-PCR of Mtor, Nlrp3, and other 22 genes associated with inflammation in rats livers after a 9-week diet...
October 2016: Immunopharmacology and Immunotoxicology
Mrinmoy Ghosh, Hyun-Woo Cho, Jeong-Woong Park, Jae-Young Choi, Young-Hwa Chung, Neelesh Sharma, Amit Kumar Singh, Nam Eun Kim, Raj Kumar Mongre, Do Huynh, Zhang Jiao Jiao, Kyoung Tag Do, Hak-Kyo Lee, Ki-Duk Song, Byung-Wook Cho, DongKee Jeong
The athletic abilities of the horse serve as a valuable model to understand the physiology and molecular mechanisms of adaptive responses to exercise. We analyzed differentially expressed genes in triceps brachii muscle tissues collected from Eonjena Taeyang and Jigusang Seryeok Thoroughbred horses and their co-expression networks in a large-scale RNA-sequence dataset comparing expression before and after exercise. High-quality horse transcriptome data were generated, with over 22 million 90-bp pair-end reads...
June 28, 2016: Applied Biochemistry and Biotechnology
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