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HIF in renal disease

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https://www.readbyqxmd.com/read/28420760/novel-lnc-rna-regulated-by-hif-1-inhibits-apoptotic-cell-death-in-the-renal-tubular-epithelial-cells-under-hypoxia
#1
Imari Mimura, Yosuke Hirakawa, Yasuharu Kanki, Natsuki Kushida, Ryo Nakaki, Yutaka Suzuki, Tetsuhiro Tanaka, Hiroyuki Aburatani, Masaomi Nangaku
Chronic tubulointerstitial hypoxia plays an important role as the final common pathway to end-stage renal disease. HIF-1 (hypoxia-inducible factor-1) is a master transcriptional factor under hypoxia, regulating downstream target genes. Genome-wide analysis of HIF-1 binding sites using high-throughput sequencers has clarified various kinds of downstream targets and made it possible to demonstrate the novel roles of HIF-1. Our aim of this study is to identify novel HIF-1 downstream epigenetic targets which may play important roles in the kidney...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28360450/renal-medullary-carcinoma-a-rare-entity
#2
Selahattin Çalışkan, Ali Murat Gökçe, Gülistan Gümrükçü, Mine Önenerk
Renal medullary carcinoma (RMC) is an uncommon aggressive neoplasm of the kidney. RMC is biologically aggressive with a very poor prognosis, and metastasis is seen in up to 95% of the patients at diagnosis or shortly thereafter. The common sites of metastasis are respectively lymph nodes, lungs, livers, and adrenal glands in order of frequency. The presence of poorly differentiated eosinophilic cells in a characteristic fibro-inflammatory stroma is seen in histological examination. The origin and pathogenesis of RMC are unclear...
March 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28331062/hypoxia-inducible-factor-1%C3%AE-activation-improves-renal-oxygenation-and-mitochondrial-function-in-early-chronic-kidney-disease
#3
Joanna L Thomas, Hai Pham, Ying Li, Elanore Hall, Guy A Perkins, Sameh S Ali, Hemal H Patel, Prabhleen Singh
Pathophysiology of chronic kidney disease (CKD) is driven by alterations in surviving nephrons to sustain renal function with ongoing nephron loss. Oxygen supply-demand mismatch, due to hemodynamic adaptations, with resultant hypoxia, plays an important role in the pathophysiology in early CKD. We sought to investigate the underlying mechanisms of this mismatch. We utilized the subtotal nephrectomy (STN) model of CKD to investigate the alterations in renal oxygenation linked to sodium (Na) transport and mitochondrial function in the surviving nephrons...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28270773/renal-hypoxia-in-ckd-pathophysiology-and-detecting-methods
#4
REVIEW
Yosuke Hirakawa, Tetsuhiro Tanaka, Masaomi Nangaku
Chronic kidney disease (CKD) is a major public health problem. Accumulating evidence suggests that CKD aggravates renal hypoxia, and in turn, renal hypoxia accelerates CKD progression. To eliminate this vicious cycle, hypoxia-related therapies, such as hypoxia-inducible factor (HIF) activation (prolyl hydroxylase domain inhibition) or NF-E2-related factor 2 activation, are currently under investigation. Clinical studies have revealed heterogeneity in renal oxygenation; therefore, the detection of patients with more hypoxic kidneys can be used to identify likely responders to hypoxia-oriented therapies...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28263291/iron-suppresses-erythropoietin-expression-via-oxidative-stress-dependent-hypoxia-inducible-factor-2-alpha-inactivation
#5
Keisuke Oshima, Yasumasa Ikeda, Yuya Horinouchi, Hiroaki Watanabe, Hirofumi Hamano, Yoshitaka Kihira, Seiji Kishi, Yuki Izawa-Ishizawa, Licht Miyamoto, Tasuku Hirayama, Hideko Nagasawa, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
Renal anemia is a major complication in chronic kidney disease (CKD). Iron supplementation, as well as erythropoiesis-stimulating agents, are widely used for treatment of renal anemia. However, excess iron causes oxidative stress via the Fenton reaction, and iron supplementation might damage remnant renal function including erythropoietin (EPO) production in CKD. EPO gene expression was suppressed in mice following direct iron treatment. Hypoxia-inducible factor-2 alpha (HIF-2α), a positive regulator of the EPO gene, was also diminished in the kidney of mice following iron treatment...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28217462/the-therapeutic-potential-of-hif-2-antagonism-in-renal-cell-carcinoma
#6
COMMENT
Olivier Cuvillier
Hypoxia, the insufficient delivery of oxygen for the demand of a tissue, contributes to the development of an aggressive phenotype, resistance to radiation therapy and chemotherapy, and is predictive of a poor outcome in numerous tumor types. Adaptation to hypoxia is mediated by hypoxia-inducible factors (HIFs), including HIF-1α and HIF-2α, which regulate genes promoting angiogenesis, increased tumor growth or metastasis. In kidney cancer, HIF-2α is believed to be the most important driver for development and progression of clear cell renal cell carcinoma (ccRCC), highlighting the therapeutic potential of HIF-2 antagonists in this disease...
February 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28181420/hypoxia-inducible-factor-1-a-urinary-biomarker-of-kidney-disease
#7
S Movafagh, D Raj, M Sanaei-Ardekani, D Bhatia, K Vo, M Mahmoudieh, R Rahman, E H Kim, A F Harralson
Identifying noninvasive biomarkers of kidney disease is valuable for diagnostic and therapeutic purposes. Hypoxia inducible factor 1 (HIF-1) expression is known to be elevated in the kidneys in several renal disease pathologies. We hypothesized that the urinary HIF-1a mRNA level may be a suitable biomarker for expression of this protein in chronic kidney disease (CKD). We compared HIF-1a mRNA levels from urine pellets of CKD and healthy subjects. To ensure that urinary HIF-1a mRNA is of kidney origin, we examined colocalization of HIF-1a mRNA with two kidney specific markers in urine cells...
February 9, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28163057/slit2-ameliorates-renal-inflammation-and-fibrosis-after-hypoxia-and-lipopolysaccharide-induced-epithelial-cells-injury-in-vitro
#8
Xiangjun Zhou, Qisheng Yao, Xinbo Sun, Xiaoxin Gong, Yong Yang, Congbo Chen, Guang Shan
Hypoxic acute kidney injury (AKI) is often incompletely repaired and leads to chronic kidney disease (CKD), which is characterized by tubulointerstitial inflammation and fibrosis. The Slit2 family of secreted glycoproteins is expressed in the kidney, it has been shown to exert an anti-inflammatory activity and prevent ischemic renal injury in vivo. However, whether Slit2 reduces renal fibrosis and inflammation after hypoxic and inflammatory epithelial cells injury in vitro remains unknown. In this study, we aimed to evaluate whether Slit2 ameliorated fibrosis and inflammation in two renal epithelial cells line challenged with hypoxia and lipopolysaccharide (LPS)...
March 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28097825/signalling-pathways-involved-in-hypoxia-induced-renal-fibrosis
#9
REVIEW
Minna Liu, Xiaoxuan Ning, Rong Li, Zhen Yang, Xiaoxia Yang, Shiren Sun, Qi Qian
Renal fibrosis is the common pathological hallmark of progressive chronic kidney disease (CKD) with diverse aetiologies. Recent researches have highlighted the critical role of hypoxia during the development of renal fibrosis as a final common pathway in end-stage kidney disease (ESKD), which joints the scientist's attention recently to exploit the molecular mechanism underlying hypoxia-induced renal fibrogenesis. The scaring formation is a multilayered cellular response and involves the regulation of multiple hypoxia-inducible signalling pathways and complex interactive networks...
January 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28054119/nitric-oxide-mediates-prolyl-hydroxylase-3-expression-in-mesangial-cells-and-in-glomerulonephritis
#10
Ahmed Aglan, Sebastian Longen, Nathalie Dehne, Yvette Köhler, Mohamed Hassan, Martina Beck, Claudia Tredup, Meike Boosen, Tzung-Harn Louise Hsieh, Liliana Schaefer, Karl-Friedrich Beck, Josef Pfeilschifter
Renal mesangial cells are regarded as main players in glomerular inflammatory diseases. To investigate a possible crosstalk between inflammatory and hypoxia-driven signaling processes, we stimulated cultured mouse mesangial cells with different inflammatory agents and analyzed the expression of prolyl hydroxylase domain containing proteins (PHDs), the main regulators of hypoxia-inducible factor (HIF) stability. Administration of IL-1β (1 nM) and TNF-α (1 nM), a combination further referred to as cytokine mix (CM), resulted in a fivefold increase in PHD3 but not PHD1 and PHD2 mRNA expression compared to untreated controls...
January 4, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27878241/hsa%C3%A2-mir%C3%A2-371%C3%A2-5p-inhibits-human-mesangial-cell-proliferation-and-promotes-apoptosis-in-lupus-nephritis-by-directly-targeting-hypoxia%C3%A2-inducible-factor-1%C3%AE
#11
Feifei Yao, Liqiu Sun, Wei Fang, Huamin Wang, Dongsheng Yao, Rui Cui, Jia Xu, Li Wang, Xiumei Wang
MicroRNAs (miRNAs/miR) have emerged as a novel class of gene expression modulators in kidney disease. Lupus nephritis (LN) is the predominant cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Hsa‑miR‑371‑5p has previously been reported to be dysregulated in LN using a miRNA microarray analysis. The present study aimed to determine the function and molecular mechanisms of hsa‑miR‑371‑5p in human mesangial cells of LN. Quantitative polymerase chain reaction (qPCR) was used to detect hsa‑miR‑371‑5p expression in LN tissues...
December 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27844272/resistance-to-targeted-therapies-in-renal-cancer-the-importance-of-changing-the-mechanism-of-action
#12
I Duran, J Lambea, P Maroto, J L González-Larriba, Luis Flores, S Granados-Principal, M Graupera, B Sáez, A Vivancos, O Casanovas
Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27774982/genetic-variation-at-the-8q24-21-renal-cancer-susceptibility-locus-affects-hif-binding-to-a-myc-enhancer
#13
Steffen Grampp, James L Platt, Victoria Lauer, Rafik Salama, Franziska Kranz, Viviana K Neumann, Sven Wach, Christine Stöhr, Arndt Hartmann, Kai-Uwe Eckardt, Peter J Ratcliffe, David R Mole, Johannes Schödel
Clear cell renal cell carcinoma (ccRCC) is characterized by loss of function of the von Hippel-Lindau tumour suppressor (VHL) and unrestrained activation of hypoxia-inducible transcription factors (HIFs). Genetic and epigenetic determinants have an impact on HIF pathways. A recent genome-wide association study on renal cancer susceptibility identified single-nucleotide polymorphisms (SNPs) in an intergenic region located between the oncogenes MYC and PVT1. Here using assays of chromatin conformation, allele-specific chromatin immunoprecipitation and genome editing, we show that HIF binding to this regulatory element is necessary to trans-activate MYC and PVT1 expression specifically in cells of renal tubular origins...
October 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27741516/senp1-promotes-proliferation-of-clear-cell-renal-cell-carcinoma-through-activation-of-glycolysis
#14
Baijun Dong, Yujing Gao, Xunlei Kang, Hongchang Gao, Jin Zhang, Hua Guo, Mingjian J You, Wei Xue, Jinke Cheng, Yiran Huang
Metabolic shift toward aerobic glycolysis is a fundamental element contributing to the development and progression of clear cell renal cell carcinoma (ccRCC). We and others previously observed enhanced glycolysis and diminished tricarboxylic acid (TCA) cycle activity in ccRCC tissue. Here, by integrated gene expression and metabolomic analyses of 36 matched pairs of tumor and adjacent normal tissues, we showed that expression of Sentrin/SUMO-specific protease 1 (SENP1) is positively associated with glycolysis levels in ccRCC...
December 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27733136/inactivation-of-the-tumor-suppressor-gene-von-hippel-lindau-vhl-in-granulocytes-contributes-to-development-of-liver-hemangiomas-in-a-mouse-model
#15
Hannah L Bader, Tien Hsu
BACKGROUND: Mutations in the tumor suppressor gene von Hippel-Lindau (VHL) underlie a hereditary cancer syndrome-VHL disease-and are also frequently observed in sporadic renal cell carcinoma of the clear cell type (ccRCC). VHL disease is characterized by malignant and benign tumors in a few specific tissues, including ccRCC, hemangioblastoma and pheochromocytoma. The etiology of these tumors remains unresolved. METHODS: Conditional inactivation of the VHL gene in mouse (Vhlh) was generated to examine the pathophysiological role of the VHL gene function...
October 12, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27678081/the-role-of-hypoxia-inducible-factor-1%C3%AE-in-zinc-oxide-nanoparticle-induced-nephrotoxicity-in-vitro-and-in-vivo
#16
Yuh-Feng Lin, I-Jen Chiu, Fong-Yu Cheng, Yu-Hsuan Lee, Ying-Jan Wang, Yung-Ho Hsu, Hui-Wen Chiu
BACKGROUND: Zinc oxide nanoparticles (ZnO NPs) are used in an increasing number of products, including rubber manufacture, cosmetics, pigments, food additives, medicine, chemical fibers and electronics. However, the molecular mechanisms underlying ZnO NP nephrotoxicity remain unclear. In this study, we evaluated the potential toxicity of ZnO NPs in kidney cells in vitro and in vivo. RESULTS: We found that ZnO NPs were apparently engulfed by the HEK-293 human embryonic kidney cells and then induced reactive oxygen species (ROS) generation...
September 27, 2016: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/27595394/targeting-renal-cell-carcinoma-with-a-hif-2-antagonist
#17
Wenfang Chen, Haley Hill, Alana Christie, Min Soo Kim, Eboni Holloman, Andrea Pavia-Jimenez, Farrah Homayoun, Yuanqing Ma, Nirav Patel, Paul Yell, Guiyang Hao, Qurratulain Yousuf, Allison Joyce, Ivan Pedrosa, Heather Geiger, He Zhang, Jenny Chang, Kevin H Gardner, Richard K Bruick, Catherine Reeves, Tae Hyun Hwang, Kevin Courtney, Eugene Frenkel, Xiankai Sun, Naseem Zojwalla, Tai Wong, James P Rizzi, Eli M Wallace, John A Josey, Yang Xie, Xian-Jin Xie, Payal Kapur, Renée M McKay, James Brugarolas
Clear cell renal cell carcinoma (ccRCC) is characterized by inactivation of the von Hippel-Lindau tumour suppressor gene (VHL). Because no other gene is mutated as frequently in ccRCC and VHL mutations are truncal, VHL inactivation is regarded as the governing event. VHL loss activates the HIF-2 transcription factor, and constitutive HIF-2 activity restores tumorigenesis in VHL-reconstituted ccRCC cells. HIF-2 has been implicated in angiogenesis and multiple other processes, but angiogenesis is the main target of drugs such as the tyrosine kinase inhibitor sunitinib...
November 3, 2016: Nature
https://www.readbyqxmd.com/read/27565965/p2y2r-is-a-direct-target-of-hif-1%C3%AE-and-mediates-secretion-dependent-cyst-growth-of-renal-cyst-forming-epithelial-cells
#18
Andre Kraus, Steffen Grampp, Margarete Goppelt-Struebe, Rainer Schreiber, Karl Kunzelmann, Dorien J M Peters, Jens Leipziger, Gunnar Schley, Johannes Schödel, Kai-Uwe Eckardt, Bjoern Buchholz
Polycystic kidney diseases are characterized by numerous renal cysts that continuously enlarge resulting in compression of intact nephrons and tissue hypoxia. Recently, we have shown that hypoxia-inducible factor (HIF)-1α promotes secretion-dependent cyst expansion, presumably by transcriptional regulation of proteins that are involved in calcium-activated chloride secretion. Here, we report that HIF-1α directly activates expression of the purinergic receptor P2Y2R in human primary renal tubular cells. In addition, we found that P2Y2R is highly expressed in cyst-lining cells of human ADPKD kidneys as well as PKD1 orthologous mouse kidneys...
December 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27537859/emerging-drugs-for-the-treatment-of-kidney-disease-induced-anemia
#19
Jolanta Malyszko, Jacek S Malyszko
INTRODUCTION: Anemia has been remained one of the most characteristic and visible manifestations of chronic renal failure. Correction of anemia requires two main treatment strategies: increased stimulation of erythropoiesis, and maintenance of an adequate iron supply to the bone marrow. AREAS COVERED: Erythropoiesis activating agents became a mainstay in the treatment of renal anemia for more than 25 years. Recently, there have been several attempts to introduce new drugs to stimulate erythropoiesis or affect the hepcidin-ferroportin pathway...
September 2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/27503806/hypoxia-inducible-factor-1%C3%AE-promotes-glomerulosclerosis-and-regulates-col1a2-expression-through-interactions-with-smad3
#20
Bethany Baumann, Tomoko Hayashida, Xiaoyan Liang, H William Schnaper
The function of hypoxia-inducible factor-1α (HIF-1α) in chronic kidney disease is disputed. Here we report that interactions of HIF-1α with transforming growth factor-β (TGF-β) signaling may promote its fibrotic effects. Knockout of HIF-1α is protective against glomerulosclerosis and glomerular type-I collagen accumulation in a mouse podocyte ablation model. Transcriptional analysis of cultured renal cells showed that α2(I) collagen expression is directly regulated by HIF-1α binding to a functional hypoxia-responsive element in its promoter at -335 relative to the transcription start site...
October 2016: Kidney International
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