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Hypoxia inducible factor

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https://www.readbyqxmd.com/read/29228345/mechanisms-and-mediators-of-hypertension-induced-by-erythropoietin-and-related-molecules
#1
Rajiv Agarwal
Hypertension is a common but frequently overlooked adverse effect of erythropoietin (EPO) therapy. Underreporting of hypertension with EPO is likely due to either more aggressively managing hypertension through the prescription of antihypertensive drugs or closer attention to dry weight. The purpose and focus of this review is to critically evaluate the mechanisms of EPO-induced hypertension. Preclinical data are considered first, followed by clinical data where available. Mediated by a variety of molecules, there is an imbalance in the vascular tone favoring net vasoconstriction that mediates EPO-induced hypertension...
December 8, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29226333/p53-and-mir-210-regulated-neurod2-a-neuronal-basic-helix-loop-helix-transcription-factor-is-downregulated-in-glioblastoma-patients-and-functions-as-a-tumor-suppressor-under-hypoxic-microenvironment
#2
Rahul Agrawal, Ankita Garg, Prit Benny Malgulwar, Vikas Sharma, Chitra Sarkar, Ritu Kulshreshtha
The factors involved in cell differentiation have recently garnered interest for their role in inhibition of pathogenesis in various tumors. However, their role in glioblastoma (GBM) remains poorly understood. We analyzed the TCGA-GBM data and found significant downregulation of neurogenic differentiation factor NeuroD2 in GBM patients. Low levels of NeuroD2 were found to be correlated with poor overall survival of GBM patients in TCGA dataset as well as in our cohort. Interestingly, NeuroD2 was shown to be transcriptionally induced by p53 and post-transcriptionally targeted by hypoxia inducible miRNA, miR-210...
December 11, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29226077/leptin-induced-migration-and-angiogenesis-in-rheumatoid-arthritis-is-mediated-by-reactive-oxygen-species
#3
Xiaotong Sun, Jing Wei, Yawei Tang, Bing Wang, Yan Zhang, Lei Shi, Jianping Guo, Fanlei Hu, Xia Li
Rheumatoid arthritis (RA) is a progressive autoimmune disease affecting the joints. In this study, we investigated the role of the pro-angiogenic factor leptin in regulating reactive oxygen species (ROS) to promote cell migration and angiogenesis in RA. We showed that leptin triggered RA fibroblast-like synoviocyte (FLS) migration by increased ROS expression. Additionally, leptin enhanced human umbilical vein endothelial cell (HUVEC) tube formation in a ROS/hypoxia-inducible factor-1α-dependent manner, accompanied by increased production of vascular endothelial growth factor and interleukin (IL)-6...
December 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29225432/molecular-docking-based-screening-of-a-simulated-hif-1-protein-model-for-potential-inhibitors
#4
Mundla Sri Latha, Madhu Sudhana Saddala
Hypoxia inducible factor-1(HIF-1) is a bHLH-family transcription factor that control genes involved in glucolysis, angiogenesis, migration, as well as invasion factors that are important for tumor progression and metastasis. HIF-1, a hetero dimer of HIF-1α and HIF-1β, binds to the hypoxia responsive genes, such as vascular endothelial growth factor (VEGF). It is one the molecular target for angiogenesis. A series of Chalcone - like compounds described that preferentially inhibit HIF-1 dimer, which can interact with amino acids within the active site of the protein...
2017: Bioinformation
https://www.readbyqxmd.com/read/29222481/hypoxia-inducible-factor-prolyl-4-hydroxylase-1-is-a-convergent-point-in-the-reciprocal-negative-regulation-of-nf-%C3%AE%C2%BAb-and-p53-signaling-pathways
#5
Karim Ullah, Ann-Helen Rosendahl, Valerio Izzi, Ulrich Bergmann, Taina Pihlajaniemi, Joni M Mäki, Johanna Myllyharju
Hypoxia-inducible factor 1α (HIF1α) induces the expression of several hundred genes in hypoxia aiming at restoration of oxygen homeostasis. HIF prolyl-4-hydroxylases (HIF-P4Hs) regulate the stability of HIF1α in an oxygen-dependent manner. Hypoxia is a common feature in inflammation and cancer and the HIF pathway is closely linked with the inflammatory NF-κB and tumor suppressor p53 pathways. Here we show that genetic inactivation or chemical inhibition of HIF-P4H-1 leads to downregulation of proinflammatory genes, while proapoptotic genes are upregulated...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222473/hypoxia-inducible-factor-1%C3%AE-is-essential-for-macrophage-mediated-erythroblast-proliferation-in-acute-friend-retrovirus-infection
#6
Timm Schreiber, Theresa Quinting, Ulf Dittmer, Joachim Fandrey, Kathrin Sutter
Macrophages are the frontline of defence against foreign microorganisms, including bacteria, parasites, and viruses. During acute viral infection, macrophages must invade the inflamed tissue toward low oxygen concentrations, where genetic cellular responses depend on hypoxia-inducible factors (HIF). In the study reported here we investigated the role of HIF-1α in macrophage function during acute retroviral infection. Wild-type and myeloid cell-specific HIF-1α knockout mice were infected with Friend retrovirus (FV), and immune response was analysed 7 and 10 days after infection...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222329/glutaminolysis-is-required-for-tgf-%C3%AE-1-induced-myofibroblast-differentiation-and-activation
#7
Karen Bernard, Naomi J Logsdon, Gloria A Benavides, Yan Sanders, Jianhua Zhang, Victor M Darley-Usmar, Victor J Thannickal
Myofibroblasts participate in physiological wound healing and pathological fibrosis.  Myofibroblast differentiation is characterized by the expression of alpha-smooth muscle actin (α-SMA) and extracellular matrix (ECM) proteins, and is dependent on metabolic reprogramming.  In this study, we explored the role of glutaminolysis and metabolites of the tricarboxylic acid cycle (TCA) in supporting myofibroblast differentiation.  Glutaminolysis converts glutamine (Gln) into alpha-ketoglutarate (α-KG), a critical intermediate in the TCA cycle...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29221952/danshensu-prevents-hypoxic-pulmonary-hypertension-in-rats-by-inhibiting-the-proliferation-of-pulmonary-artery-smooth-muscle-cells-via-tgf-%C3%AE-smad3-associated-pathway
#8
Ning Zhang, Mingqing Dong, Ying Luo, Feng Zhao, Yongjun Li
Hypoxic pulmonary hypertension is characterized by the remodeling of pulmonary artery. Previously we showed that tanshinone IIA, one lipid-soluble component from the Chinese herb Danshen, ameliorated hypoxic pulmonary hypertension by inhibiting pulmonary artery remodeling. Here we explored the effects of danshensu, one water-soluble component of Danshen, on hypoxic pulmonary hypertension and its mechanism. Rats were exposed to hypobaric hypoxia for 4 weeks to develop hypoxic pulmonary hypertension along with administration of danshensu...
December 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29221165/angiogenesis-in-adenosquamous-cancer-of-pancreas
#9
Nicola Silvestris, Katia Danza, Vito Longo, Oronzo Brunetti, Livia Fucci, Antonella Argentiero, Angela Calabrese, Ivana Cataldo, Roberto Tamma, Domenico Ribatti, Stefania Tommasi
Adenosquamous carcinoma of the pancreas (ASCP) is an uncommon variant of exocrine pancreatic malignancies, characterized by a histological admixture of adenomatous and squamous cell elements. This cancer is characterized by a poorly differentiated histology and a poorer clinical outcome compared to pancreatic ductal adenocarcinoma (PDAC). Unlike PDAC, that is characterized by a low microvascular density (MVD) and collapsed vasculature, no data are available about angiogenesis in ASPC. Immunohistochemical evaluation of MVD and trypatse-positive mast cells (MCs) were performed on a single case of ASCP compared to PDAC...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218693/non-catalytic-region-of-tyrosine-kinase-adaptor-protein-2-nck2-pathways-as-factor-promoting-aggressiveness-in-ovarian-cancer
#10
Mara Fanelli, Alessia Camperchioli, Lella Petrella, Marco Petrillo, Cinzia Baranello, Pina Baccaro, Carmela Paolillo, Ettore Capoluongo, Giovanni Scambia
BACKGROUND: In this study we investigated the function of the non-catalytic region of tyrosine kinase adaptor protein 2 (NCK2) and its correlation with ITGB1 and ITGB4 integrins in driving ovarian cancer (OvCa) aggressiveness. We also evaluated whether NCK2 may influence prognosis in OvCa patients. METHODS: Nanofluidic technology was used to analyze expression of NCK2 in 332 OvCa patients. To evaluate mRNA expression of NCK2, integrins and VEGFA in OvCa cell lines, qRT-PCR was performed...
December 5, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/29218250/evaluation-of-the-role-of-downregulation-of-snf5-ini1-core-subunit-of-swi-snf-complex-in-clear-cell-renal-cell-carcinoma-development
#11
Elzbieta Sarnowska, Michal Szymanski, Nataliia Rusetska, Marcin Ligaj, Iga Jancewicz, Pawel Cwiek, Marta Skrodzka, Marcin Leszczynski, Joanna Szarkowska, Alicja Chrzan, Malgorzata Stachowiak, Jaroslaw Steciuk, Anna Maassen, Lech Galek, Tomasz Demkow, Janusz A Siedlecki, Tomasz J Sarnowski
Clear cell renal cell carcinoma (ccRCC) is characterized by stabilization of hypoxia-inducible factor (HIF1), and mutations in von Hippel-Lindau (VHL) gene. Additionally, in about 40% of ccRCC cases the mutation in PBRM1 (POLYBROMO1) gene coding for a non-core subunit of SWI/SNF chromatin remodeling complex was found suggesting potential impairment of this complex function in ccRCC. In this study we assessed the extent to which the core SWI/SNF complex subunit - INI1 (hSNF5/SMARCB1) is affected in ccRCC and whether it has any consequences on the development of this type of cancer...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29218074/autophagy-in-endometriosis
#12
REVIEW
Hui-Li Yang, Jie Mei, Kai-Kai Chang, Wen-Jie Zhou, Li-Qing Huang, Ming-Qing Li
Endometriosis (EMS) is a common gynecologic disease that causes chronic pelvic pain, dysmenorrhea, and infertility in women. The doctrine of menstruation back flow planting and defects in the immune system are well known and widely accepted. In recent years, increasing studies have been focused on the role of autophagy in EMS, and have shown that autophagy plays a vital role in EMS. Autophagy, which is known as the non-apoptotic form of programmed cell death induced by a large number of intracellular/extracellular stimuli, is the major cellular pathway for the degradation of long-lived proteins and cytoplasmic organelles in eukaryotic cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29216640/celecoxib-down-regulates-the-hypoxia-induced-expression-of-hif-1%C3%AE-and-vegf-through-the-pi3k-akt-pathway-in-retinal-pigment-epithelial-cells
#13
Yi-Zhou Sun, Na Cai, Ning-Ning Liu
BACKGROUND/AIMS: The goal of this study was to detect the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal pigmented epithelial (RPE) cells treated with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, under hypoxic and normoxic conditions and to explore the signaling mechanism involved in regulating the hypoxia-induced expression of HIF-1α and VEGF in RPE cells. METHODS: D407 cells were cultured in normoxic or hypoxic conditions, with or without celecoxib or a PI3K inhibitor (LY294002)...
December 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29216379/endothelial-cell-differentiation-is-encompassed-by-changes-in-long-range-interactions-between-inactive-chromatin-regions
#14
Henri Niskanen, Irina Tuszynska, Rafal Zaborowski, Merja Heinäniemi, Seppo Ylä-Herttuala, Bartek Wilczynski, Minna U Kaikkonen
Endothelial cells (ECs) differentiate from mesodermal progenitors during vasculogenesis. By comparing changes in chromatin interactions between human umbilical vein ECs, embryonic stem cells and mesendoderm cells, we identified regions exhibiting EC-specific compartmentalization and changes in the degree of connectivity within topologically associated domains (TADs). These regions were characterized by EC-specific transcription, binding of lineage-determining transcription factors and cohesin. In addition, we identified 1200 EC-specific long-range interactions (LRIs) between TADs...
December 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29215742/effects-of-small-interfering-rna-targeting-tlr4-on-expressions-of-adipocytokines-in-obstructive-sleep-apnea-hyponea-syndrome-with-hypertension-in-a-rat-model
#15
Jing-Guo Wu, Nan Xun, Li-Jin Zeng, Zhen-Yu Li, Yan-Bing Liang, Hao Tang, Zhong-Fu Ma
We explored the effects of RNA interference-mediated silencing of TLR4 gene on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome (OSAS) with hypertension in a rat model. Systolic blood pressure of caudal artery and physiological changes were observed when establishing rat models of OSAS with hypertension. Mature rat adipocytes were induced from separated and cultured primary rat adipocytes. To transfect rat mature adipocytes, TLR4 siRNA group and negative control (NC) siRNA group were established...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29215599/systematic-analysis-of-transcriptomic-profile-of-renal-cell-carcinoma-under-long-term-hypoxia-using-next-generation-sequencing-and-bioinformatics
#16
Szu-Chia Chen, Feng-Wei Chen, Ya-Ling Hsu, Po-Lin Kuo
Patients with clear cell renal cell carcinoma (ccRCC) are often diagnosed with both von Hippel-Lindau (VHL) mutations and the constitutive activation of hypoxia-inducible factor-dependent signaling. In this study, we investigated the effects of long-term hypoxia in 786-O, a VHL-defective renal cell carcinoma cell line, to identify potential genes and microRNAs associated with tumor malignancy. The transcriptomic profiles of 786-O under normoxia, short-term hypoxia and long-term hypoxia were analyzed using next-generation sequencing...
December 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29212832/adenosine-a-2a-receptor-agonist-2-p-2-carboxyethyl-phenethylamino-5-n-ethylcarboxamidoadenosine-hydrochloride-hydrate-cgs21680-inhibits-inflammation-and-increases-fibroblast-growth-factor-2-fgf-2-tissue-expression-in-carrageenan-induced-rat-paw-edema
#17
Armando Ialenti, Elisabetta Caiazzo, Silvana Morello, Rosa Carnuccio, Carla Cicala
Adenosine is the final product of ATP metabolism, mainly derived from the action of 5'-nucleotidase cleavage of AMP. Cellular production of adenosine is greatly enhanced in inflamed tissues, ischemic tissues and under hypoxia, where ATP is released from damaged cells. Much evidence has been accumulated on adenosine antinflammatory effects mediated through A 2A receptor activation; A2A adenosine receptor has also been shown to play a role in matrix deposition and wound healing in a damaged tissue, contributing to dermal tissue protection and repair...
December 6, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29212800/extracellular-retention-of-pdgf-b-directs-vascular-remodeling-in-mouse-hypoxia-induced-pulmonary-hypertension
#18
Philip Tannenberg, Ya-Ting Chang, Lars Muhl, Bàrbara Laviña, Hanna Gladh, Guillem Genové, Christer Betsholtz, Erika Folestad, Karin Tran-Lundmark
Pulmonary hypertension (PH) is a lethal condition and current vasodilator therapy has limited effect. Anti-proliferative strategies targeting platelet-derived growth factor (PDGF) receptors, such as imatinib, have generated promising results in animal studies. Imatinib is however a non-specific tyrosine kinase inhibitor and has in clinical studies caused unacceptable adverse events. Further studies are needed on the role of PDGF signaling in PH. Here, mice expressing a variant of PDGF-B with no retention motif (Pdgfbret/ret), resulting in defective binding to extracellular matrix, were studied...
December 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29212519/gper-mediates-the-angiocrine-actions-induced-by-igf1-through-the-hif-1%C3%AE-vegf-pathway-in-the-breast-tumor-microenvironment
#19
Ernestina M De Francesco, Andrew H Sims, Marcello Maggiolini, Federica Sotgia, Michael P Lisanti, Robert B Clarke
BACKGROUND: The G protein estrogen receptor GPER/GPR30 mediates estrogen action in breast cancer cells as well as in breast cancer-associated fibroblasts (CAFs), which are key components of microenvironment driving tumor progression. GPER is a transcriptional target of hypoxia inducible factor 1 alpha (HIF-1α) and activates VEGF expression and angiogenesis in hypoxic breast tumor microenvironment. Furthermore, IGF1/IGF1R signaling, which has angiogenic effects, has been shown to activate GPER in breast cancer cells...
December 6, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29212263/combination-of-betulinic-acid-and-chidamide-inhibits-acute-myeloid-leukemia-by-suppression-of-the-hif1%C3%AE-pathway-and-generation-of-reactive-oxygen-species
#20
Hongyu Zhang, Ling Li, Min Li, Xiaodong Huang, Weiguo Xie, Wei Xiang, Paul Yao
Acute myeloid leukemia (AML) is a heterogeneous disorder of the hematopoietic system with no common genetic "Achilles heel" that can be targeted. Most patients respond well to standard therapy, while a majority relapse, and development of an effective therapy for AML patients is still urgently needed. In this study, we demonstrated that betulinic acid (BA) significantly increased Aryl hydrocarbon receptor (AHR) expression through demethylation on the AHR promoter in AML cells, and the increased AHR expression interacts with and sequesters ARNT, subsequently suppressing hypoxia-inducible factor-1α (HIF1α) pathway...
November 7, 2017: Oncotarget
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