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Hypoxia induced factor

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https://www.readbyqxmd.com/read/28938402/the-pathophysiological-sequence-of-glucocorticoid-induced-osteonecrosis-of-the-femoral-head-in-male-mice
#1
Robert S Weinstein, Erin A Hogan, Michael J Borrelli, Serguei Liachenko, Charles A O'Brien, Stavros C Manolagas
In search of the sequence of pathogenic events leading to glucocorticoid-induced osteonecrosis, we determined the molecular, biomechanical, cellular, and vascular changes in the femur of C57BL/6 mice receiving prednisolone for 14, 28 or 42 days. The femoral head, but not the distal femur, of mice treated for 14 days showed a decrease in the expression of the hypoxia-inducible factor (Hif-1α) and vascular endothelial growth factor (VEGF), the number of osteoblasts, bone formation rate and strength and an increase in osteoclasts...
September 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28937825/tanshinone-iia-inhibits-vegf-secretion-and-hif-1%C3%AE-expression-in-cultured-human-retinal-pigment-epithelial-cells-under-hypoxia
#2
Rami M Alzhrani, Qasim Alhadidi, Rinda Devi Bachu, Zahoor Shah, Surajit Dey, Sai Hs Boddu
PURPOSE: The current work intends to study the activity of tanshinone IIA on secretion of vascular endothelial growth factor (VEGF) and expression of hypoxia inducible factor 1α (HIF-1α) in human retinal pigment epithelial cells (ARPE-19 cells) under hypoxic condition. METHODS: The cytotoxicity of tanshinone IIA was tested in ARPE-19 cells by MTT assay. ARPE-19 cells were incubated with different concentrations of cobalt chloride (100, 150, and 200 µM) for 12 h, and levels of expressed HIF-1α and secreted VEGF were quantified through Western blot and ELISA, respectively...
September 22, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28936211/regulation-of-human-macrophage-m1-m2-polarization-balance-by-hypoxia-and-the-triggering-receptor-expressed-on-myeloid-cells-1
#3
Federica Raggi, Simone Pelassa, Daniele Pierobon, Federica Penco, Marco Gattorno, Francesco Novelli, Alessandra Eva, Luigi Varesio, Mirella Giovarelli, Maria Carla Bosco
Macrophages (Mf) are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1) and alternatively activated (anti-inflammatory M2) subsets...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28928465/endothelial-adenosine-a2a-receptor-mediated-glycolysis-is-essential-for-pathological-retinal-angiogenesis
#4
Zhiping Liu, Siyuan Yan, Jiaojiao Wang, Yiming Xu, Yong Wang, Shuya Zhang, Xizhen Xu, Qiuhua Yang, Xianqiu Zeng, Yaqi Zhou, Xuejiao Gu, Sarah Lu, Zhongjie Fu, David J Fulton, Neal L Weintraub, Ruth B Caldwell, Wenbo Zhang, Chaodong Wu, Xiao-Ling Liu, Jiang-Fan Chen, Aftab Ahmad, Ismail Kaddour-Djebbar, Mohamed Al-Shabrawey, Qinkai Li, Xuejun Jiang, Ye Sun, Akrit Sodhi, Lois Smith, Mei Hong, Yuqing Huo
Adenosine/adenosine receptor-mediated signaling has been implicated in the development of various ischemic diseases, including ischemic retinopathies. Here, we show that the adenosine A2a receptor (ADORA2A) promotes hypoxia-inducible transcription factor-1 (HIF-1)-dependent endothelial cell glycolysis, which is crucial for pathological angiogenesis in proliferative retinopathies. Adora2a expression is markedly increased in the retina of mice with oxygen-induced retinopathy (OIR). Endothelial cell-specific, but not macrophage-specific Adora2a deletion decreases key glycolytic enzymes and reduces pathological neovascularization in the OIR mice...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928383/human-stem-cells-alter-the-invasive-properties-of-somatic-cells-via-paracrine-activation-of-mtorc1
#5
Margit Rosner, Ha Thi Thanh Pham, Richard Moriggl, Markus Hengstschläger
Controlled invasion is essential during many physiological processes, whereas its deregulation is a hallmark of cancer. Here we demonstrate that embryonic, induced pluripotent and amniotic fluid stem cells share the property to induce the invasion of primary somatic cells of various origins through insulin-like growth factor I (IGF-I)- or II (IGF-II)-mediated paracrine activation of mechanistic target of rapamycin complex 1 (mTORC1). We propose a model in which downstream of mTORC1 this stem cell-induced invasion is mediated by hypoxia-inducible factor 1-alpha (HIF-1α)-regulated matrix metalloproteinases...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928287/hif-3%C3%AE-promotes-metastatic-phenotypes-in-pancreatic-cancer-by-transcriptional-regulation-of-the-rhoc-rock1-signaling-pathway
#6
Xianfei Zhou, Xingjun Guo, Meiyuan Chen, Chencheng Xie, Jianxin Jiang
Hypoxia contributes to pancreatic cancer progression and promotes its growth and invasion. Previous research principally focused on hypoxia-inducible factor-1 alpha and HIF-2α (HIF1A and EPAS1) as the major hypoxia-associated transcription factors in pancreatic cancer. However, the role of HIF-3α (HIF3A) has not been investigated. Therefore, HIF-1α, HIF-2α, and HIF-3α expression levels were measured under normoxic and hypoxic conditions. In addition, HIF-3α expression was measured in human pancreatic cancer tissue specimens and the impact of altered HIF-3α expression on cell invasion and migration was investigated in vitro and in vivo, as well as the underlying mechanisms...
September 19, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28928136/endothelial-epas1-deficiency-is-sufficient-to-promote-parietal-epithelial-cell-activation-and-fsgs-in-experimental-hypertension
#7
Yosu Luque, Olivia Lenoir, Philippe Bonnin, Lise Hardy, Anna Chipont, Sandrine Placier, Sophie Vandermeersch, Yi-Chun Xu-Dubois, Blaise Robin, Hélène Lazareth, Michèle Souyri, Léa Guyonnet, Véronique Baudrie, Eric Camerer, Eric Rondeau, Laurent Mesnard, Pierre-Louis Tharaux
FSGS, the most common primary glomerular disorder causing ESRD, is a complex disease that is only partially understood. Progressive sclerosis is a hallmark of FSGS, and genetic tracing studies have shown that parietal epithelial cells participate in the formation of sclerotic lesions. The loss of podocytes triggers a focal activation of parietal epithelial cells, which subsequently form cellular adhesions with the capillary tuft. However, in the absence of intrinsic podocyte alterations, the origin of the pathogenic signal that triggers parietal epithelial cell recruitment remains elusive...
September 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28928122/discovery-and-preclinical-characterization-of-gsk1278863-daprodustat-a-small-molecule-hypoxia-inducible-factor-hif-prolyl-hydroxylase-inhibitor-for-anemia
#8
Jennifer L Ariazi, Kevin J Duffy, David F Adams, Duke M Fitch, Lusong Luo, Melissa Pappalardi, Mangatt Biju, Erin Hugger DiFilippo, Tony Shaw, Ken Wiggall, Connie Erickson-Miller
Decreased erythropoietin (EPO) production, shortened erythrocyte survival, and other factors reducing the response to EPO contribute to anemia in patients with a variety of underlying pathologies such as chronic kidney disease (CKD). Treatment with recombinant human EPO (rHuEPO) at supraphysiological concentrations has proven to be efficacious. However, it does not ameliorate the condition in all patients and presents its own risks, including cardiovascular complications. The transcription factors hypoxia-inducible factor (HIF)1α and HIF2α control the physiological response to hypoxia and invoke a program of increased erythropoeisis...
September 19, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28928094/identification-of-hypoxia-regulated-angiogeneic-genes-in-colorectal-cancer
#9
Shaoqi Zong, Wen Li, Hongjia Li, Susu Han, Shanshan Liu, Qi Shi, Fenggang Hou
The tumour hypoxia would trigger the angiogenesis switch for survival, and increase the ability of cancer cells to invade and metastasis. However, hypoxia regulated genes that invovled in angiogenesis in colorectal cancer (CRC) have not been explored in detail. The aim of this study was to explore angiogenic genes under hypoxia condition in CRC. Here, we found that endothelial cells tube formation and cancer cells invasion ability were promoted even under chronic hypoxia condition (72 h) in colon adenocarcinoma HCT-116 cells...
September 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28927682/mgf-e-peptide-pretreatment-improves-the-proliferation-and-osteogenic-differentiation-of-bmscs-via-mek-erk1-2-and-pi3k-akt-pathway-under-severe-hypoxia
#10
Yongqiang Sha, Yonggang Lv, Zhiling Xu, Li Yang, Xiaoying Hao, Ruli Afandi
AIMS: Severe hypoxia always inhibits the cell proliferation, osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), and hinders bone defect repair. Herein we explored the effects of mechano-growth factor (MGF) E peptide on the proliferation and osteogenic differentiation of BMSCs under severe hypoxia. MATERIALS AND METHODS: CoCl2 was utilized to simulate severe hypoxia. MTS was used to detect cell viability. Cell proliferation was verified through flow cytometry and EdU assay...
September 16, 2017: Life Sciences
https://www.readbyqxmd.com/read/28927334/evaluation-of-xenogeneic-extracellular-matrix-fabricated-from-cucl2-conditioned-mesenchymal-stem-cell-sheets-as-a-bioactive-wound-dressing-material
#11
Hui-Cong Du, Lin Jiang, Wen-Xin Geng, Jing Li, Rui Zhang, Jin-Ge Dang, Mao-Guo Shu, Li-Wen Li
The extracellular matrix has drawn considerable interest in tissue engineering not only acts as a bioactive three-dimensional scaffold but also regulates cell behaviors through providing biochemical signals. Extracellular matrix-based biomaterials, mainly derived from xenogeneic tissues, have shown positive outcomes in promoting cutaneous wound healing. However, such extracellular matrices only contain low doses of growth factors, which limit their therapeutic efficiency. Recent reports demonstrated that cell sheets made from mesenchymal stem cell can accelerate wound repair through enhanced re-epithelialization and angiogenesis, but its clinical translation is hindered by several limitations, such as the risk of aberrant immune responses and cost implications...
January 1, 2017: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/28927155/ras-protein-activator-like-1-is-functionally-involved-in-hypoxia-resistance-in-breast-cancer-cells-by-targeting-hypoxia-inducible-factor-1%C3%AE
#12
Ziming Huang, Rong Wang, Gang Wei, Ran Jiang, Yuan Zheng, Yiwen Tian, Bo Chen, Chunmei Ye, Mingxing Xue, Chunjiao Yu
RAS protein activator-like 1 (RASAL1) is a member of the RAS GTPase-activating protein family, and previous studies indicate that RASAL1 is involved in the progression of hypoxia resistance in breast cancer cells. In the present study, increased levels of hypoxia inducible factor-1α (HIF-1α) were observed to be accompanied with increased expression of RASAL1 in the breast cancer cell lines MCF-7 and MDA-MB-231 cells under hypoxia. Based on this, it was postulated that RASAL1 may serve a functional role in the development of hypoxia resistant in breast cancer cells...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926527/genistein-suppresses-aerobic-glycolysis-and-induces-hepatocellular-carcinoma-cell-death
#13
Sainan Li, Jingjing Li, Weiqi Dai, Qinghui Zhang, Jiao Feng, Liwei Wu, Tong Liu, Qiang Yu, Shizan Xu, Wenwen Wang, Xiya Lu, Kan Chen, Yujing Xia, Jie Lu, Yingqun Zhou, Xiaoming Fan, Wenhui Mo, Ling Xu, Chuanyong Guo
BACKGROUND: Genistein is a natural isoflavone with many health benefits, including antitumour effects. Increased hypoxia-inducible factor 1 α (HIF-1α) levels and glycolysis in tumour cells are associated with an increased risk of mortality, cancer progression, and resistance to therapy. However, the effect of genistein on HIF-1α and glycolysis in hepatocellular carcinoma (HCC) is still unclear. METHODS: Cell viability, apoptosis rate, lactate production, and glucose uptake were measured in HCC cell lines with genistein incubation...
September 19, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28925921/au-pt-nanoparticles-as-catalase-mimics-to-attenuate-tumor-hypoxia-and-enhance-immune-cell-mediated-cytotoxicity
#14
Juan Li, Hong Liang, Ying Wu, Xiang-Yu Ou, Jingying Li
Hypoxic tumor microenvironment (TME) is closely linked to tumor progression, heterogeneity and immune suppression. Therefore, the development of effective methods to overcome hypoxia and substantially enhance the immunotherapy efficacy remains a desirable goal. Herein, we engineered a biocompatible Au core/Pt shell nanoparticles (Au@Pt NPs) to reoxygenate the TME by reacting with endogenous H2O2. Treatment with Au@Pt NPs appeared to improve oxygen in intracellular environments and decrease hypoxia-inducible factor (HIF)-1α expression...
September 19, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28925578/combined-fetal-inflammation-and-postnatal-hypoxia-causes-myelin-deficits-and-autism-like-behavior-in-a-rat-model-of-diffuse-white-matter-injury
#15
Erik van Tilborg, E J Marijke Achterberg, Caren M van Kammen, Annette van der Toorn, Floris Groenendaal, Rick M Dijkhuizen, Cobi J Heijnen, Louk J M J Vanderschuren, Manon N J L Benders, Cora H A Nijboer
Diffuse white matter injury (WMI) is a serious problem in extremely preterm infants, and is associated with adverse neurodevelopmental outcome, including cognitive impairments and an increased risk of autism-spectrum disorders. Important risk factors include fetal or perinatal inflammatory insults and fluctuating cerebral oxygenation. However, the exact mechanisms underlying diffuse WMI are not fully understood and no treatment options are currently available. The use of clinically relevant animal models is crucial to advance knowledge on the pathophysiology of diffuse WMI, allowing the definition of novel therapeutic targets...
September 19, 2017: Glia
https://www.readbyqxmd.com/read/28925400/the-hif-and-other-quandaries-in-vhl-disease
#16
REVIEW
D Tarade, M Ohh
Mutations in VHL underlie von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome with several subtypes depending on the risk of developing certain combination of classic features, such as clear cell renal cell carcinoma (ccRCC), hemangioblastoma and pheochromocytoma. Although numerous potential substrates and functions of pVHL have been described over the past decade, the best-defined role of pVHL has remained as the negative regulator of the heterodimeric hypoxia-inducible factor (HIF) transcription factor via the oxygen-dependent ubiquitin-mediated degradation of HIF-α subunit...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28925397/coactosin-like-protein-clp-cotl1-suppresses-breast-cancer-growth-through-activation-of-il-24-perp-and-inhibition-of-non-canonical-tgf%C3%AE-signaling
#17
L Xia, X Xiao, W L Liu, Y Song, T J J Liu, Y J Li, E Zacksenhaus, X J Hao, Y Ben-David
Coactosin-like protein (CLP, or Cotl1), is an F-actin-binding protein, whose role in cancer is largely unknown. Here we show that CLP/Cotl1 is highly expressed in a rat epithelial breast cancer cell line (FE1.3) compared with its mesenchymal counterpart (FE1.2). Knockdown of CLP/Cotl1 in FE1.3 cells increased cell proliferation, whereas its overexpression in FE1.2 cells inhibited proliferation in culture and reduced tumor growth in xenograft assays in mice. Mechanistically, we identified two major pathways through which CLP/Cotl1 exerts its suppressive effects...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28924365/effects-of-hypobaric-hypoxia-on-rat-retina-and-protective-response-of-resveratrol-to-the-stress
#18
Xiaorong Xin, Hong Dang, Xiaojing Zhao, Haohao Wang
High-altitude retinopathy represents retinal functional changes associated with environmental challenges imposed by hypobaric hypoxia, but the detailed cellular and molecular mechanism underlying this process remains unclear. Our current investigation was to explore the effect of hypobaric hypoxia on the rat retina and determine whether resveratrol has a protective efficacy on the hypoxic damage to the retina. Experiment rats were randomly grouped as the control group, hypoxia group and resveratrol intervention group...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28924179/detrimental-effect-of-hypoxia-inducible-factor-1%C3%AE-induced-autophagy-on-multiterritory-perforator-flap-survival-in-rats
#19
Long Wang, Zhicheng Jin, Jieke Wang, Shao Chen, Li Dai, Dingsheng Lin, Lingfeng Wu, Weiyang Gao
Hypoxia-inducible factor-1α (HIF-1α) plays a key role in angiogenesis, improves flap survival, and activates autophagy. The effect of HIF-1α-induced autophagy is still debatable. Thus, we investigated the effect of HIF-1α-induced autophagy on multiterritory perforator flap survival. In this study, 99 male Sprague-Dawley rats received multiterritory perforator flap procedure and were divided into three groups with 33 each. The dimethyloxalylglycine (DMOG) plus 3-methyladenine (3-MA) group received intraperitoneal injection of DMOG (40 mg/kg) and 3-MA (10 mg/kg)...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923650/does-renal-tubular-injury-induced-local-tissue-hypoxia-involve-post-transplantation-erythrocytosis
#20
A Unal, S Ata, C Karakurkcu, M Z Ciraci, I Kocyigit, M H Sipahioglu, B Tokgoz, O Oymak
BACKGROUND: The pathogenesis of post-transplantation erythrocytosis (PTE) is not well understood and appears to be multifactorial. Our hypothesis in this study was that several factors, including toxicity of calcineurin inhibitor, immunologic factors, and chronic allograft nephropathy, can trigger local tissue hypoxia in peritubular interstitium, which is where production of erythropoietin (EPO) takes place. This local interstitial tissue hypoxia can cause an increase in renal EPO production, which induces the development of PTE...
October 2017: Transplantation Proceedings
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