scholarly journals Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFβ3

2000 ◽  
Vol 105 (5) ◽  
pp. 577-587 ◽  
Author(s):  
Isabella Caniggia ◽  
Homa Mostachfi ◽  
Jennifer Winter ◽  
Max Gassmann ◽  
Stephen J. Lye ◽  
...  
Keyword(s):  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Trophoblast Differentiation ◽  
Human Trophoblast ◽  
Hypoxia Inducible Factor 1

scholarly journals Down-regulation of microRNA-31 suppresses hepatic fibrosis induced by carbon tetrachloride

2020 ◽  
Vol 18 ◽  
pp. 205873922094263
Author(s):  
Bing Deng ◽  
Detao Tang ◽  
Yong Qiang ◽  
Xiang Zheng
Keyword(s):  
Carbon Tetrachloride ◽  
Olive Oil ◽  
Hepatic Fibrosis ◽  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Related Factor ◽  
Related Factors ◽  
Altered Expression ◽  
Cell Functions ◽  
Hypoxia Inducible Factor 1

MicroRNA-31 (miR-31) is among the most frequently altered microRNAs in human diseases, and altered expression of miR-31 has been detected in a large variety of diseases types. miR-31 could also regulate a variety of cell functions including hepatic fibrosis. Hepatic stellate cells (HSCs) are regarded as the major cell type involved in hepatic fibrosis. Male BALB/c mice (five mice per group aged 6 weeks) received 200 μL of body weight of carbon tetrachloride (10% CCl4) mixed with olive oil intraperitoneally, and the first dose was doubled. To induce hepatic fibrosis, carbon tetrachloride was injected twice a week for 4, 6, 8, and 10 weeks. Control animals were injected with an equal volume of olive oil at the same time intervals. We found that miR-31 expression and fibrosis-related factors in four hepatic fibrosis stages. However, we noted that inhibition of miR-31 was down-regulated fibrosis-related factor expression in F1–F3 stages, but no F4 stage. Thus, we hypothesize that miR-31 may mediate hepatic fibrosis. In this research, we found that inhibition of miR-31 expression significantly inhibited HSC activation. The biological function of miR-31 during HSC activation might be through targeting hypoxia-inducible factor 1-alpha inhibitor (HIF1AN). Inhibition of miR-31 can reduce the transcription factor activity of hypoxia inducible factor 1 (HIF-1) by targeting the biological effects of HIF1AN with the condition of hypoxia. In later hepatic fibrosis could be rescue combining with inhibition of miR-31 and adding heparin-binding EGF-like growth factor (HBEGF).

scholarly journals Intermittent hypoxia enhances the expression of HIF1A by increasing the quantity and catalytic activity of KDM4A-C and demethylating H3K9me3 at the HIF1A locus

2021 ◽  
Author(s):  
Chloe-Anne Martinez ◽  
Neha Bal ◽  
Peter A Cistulli ◽  
Kristina M Cook
Keyword(s):  
Intermittent Hypoxia ◽  
Target Genes ◽  
Chronic Hypoxia ◽  
Oxygen Sensing ◽  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Sensing Systems ◽  
Cellular Oxygen ◽  
Fine Tune

Cellular oxygen-sensing pathways are primarily regulated by hypoxia inducible factor-1 (HIF-1) in chronic hypoxia and are well studied. Intermittent hypoxia also occurs in many pathological conditions, yet little is known about its biological effects. In this study, we investigated how two proposed cellular oxygen sensing systems, HIF-1 and KDM4A-C, respond to cells exposed to intermittent hypoxia and compared to chronic hypoxia. We found that intermittent hypoxia increases HIF-1 activity through a pathway distinct from chronic hypoxia, involving the KDM4A, -B and -C histone lysine demethylases. Intermittent hypoxia increases the quantity and activity of KDM4A-C resulting in a decrease in H3K9 methylation. This contrasts with chronic hypoxia, which decreases KDM4A-C activity, leading to hypermethylation of H3K9. Demethylation of histones bound to the HIF1A gene in intermittent hypoxia increases HIF1A mRNA expression, which has the downstream effect of increasing overall HIF-1 activity and expression of HIF target genes. This study highlights how multiple oxygen-sensing pathways can interact to regulate and fine tune the cellular hypoxic response depending on the period and length of hypoxia.

scholarly journals Hypoxia-Inducible Factor-1 Transactivates Transforming Growth Factor-β3 in Trophoblast

Endocrinology ◽  
2004 ◽  
Vol 145 (9) ◽  
pp. 4113-4118 ◽  
Author(s):  
Hirotaka Nishi ◽  
Toshihide Nakada ◽  
Mitsuyasu Hokamura ◽  
Yumi Osakabe ◽  
Osamu Itokazu ◽  
...  
Keyword(s):  
Promoter Activity ◽  
Transforming Growth Factor ◽  
Hypoxia Inducible Factor ◽  
First Trimester ◽  
Vital Role ◽  
Low Oxygen ◽  
Mobility Shift ◽  
Trophoblast Differentiation ◽  
Hypoxia Inducible Factor 1 ◽  
Electrophoretic Mobility Shift Assays

Abstract Hypoxia occurs during the development of placenta in the first trimester and is implicated in trophoblast differentiation. Intervillous blood flow increases after 10 wk of gestation and results in exposure of trophoblast cells to oxygen. Before this time, low oxygen appears to prevent trophoblast differentiation toward an invasive phenotype. The oxygen-regulated early events of trophoblast differentiation are mediated by TGF-β3. TGF-β3 plays a vital role in trophoblast differentiation, and its overexpression can be found in preeclamptic placenta. We sought to determine the mechanism of TGF-β3 expression through hypoxia-inducible factor (HIF)-1. We show that HIF-1α and TGF-β3 are overexpressed in preeclamptic placenta. Hypoxia not only transactivates the TGF-β3 promoter activity but also enhances endogenous TGF-β3 expression. Using the TGF-β3 promoter deletion mutants, we show that the region between −90 and −60, which contains a putative HIF-1 consensus motif, is crucial for HIF-1-mediated transactivation. Electrophoretic mobility shift assays show that HIF-1 binds to the oligonucleotide containing the HIF-1 motif. Also, introduction of an antisense oligonucleotide for HIF-1 diminishes TGF-β3 expression during hypoxia, indicating that the up-regulation of TGF-β3 by hypoxia is mediated through HIF-1. Our results provide evidence that regulation of TGF-β3 promoter activity by HIF-1 represents a mechanism for trophoblast differentiation during hypoxia.

HYPOXIA INDUCIBLE FACTOR-1 ALPHA IMPAIRS SYNCYTIALIZATION OF HUMAN TROPHOBLAST BEWO CELLS: ROLE OF ENDOCANNABINOID SYSTEM.

Placenta ◽  
2019 ◽  
Vol 83 ◽  
pp. e22
Author(s):  
Tomás Etcheverry ◽  
Paula Accialini ◽  
Marcos Palligas ◽  
Cyntia Abán ◽  
Nora Saraco ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Endocannabinoid System ◽  
Human Trophoblast ◽  
Hypoxia Inducible Factor 1 ◽  
Bewo Cells

scholarly journals The Role of Hypoxia Inducible Factor-1 in Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Dongjun Luo ◽  
Zhongxia Wang ◽  
Junyi Wu ◽  
Chunping Jiang ◽  
Junhua Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Chemotherapy Resistance ◽  
Therapy Resistance ◽  
Hypoxia Inducible Factor 1 ◽  
New Therapeutic Approaches ◽  
High Level

Hypoxia is a common feature of many solid tumors, including hepatocellular carcinoma (HCC). Hypoxia can promote tumor progression and induce radiation and chemotherapy resistance. As one of the major mediators of hypoxic response, hypoxia inducible factor-1 (HIF-1) has been shown to activate hypoxia-responsive genes, which are involved in multiple aspects of tumorigenesis and cancer progression, including proliferation, metabolism, angiogenesis, invasion, metastasis and therapy resistance. It has been demonstrated that a high level of HIF-1 in the HCC microenvironment leads to enhanced proliferation and survival of HCC cells. Accordingly, overexpression, of HIF-1 is associated with poor prognosis in HCC. In this review, we described the mechanism by which HIF-1 is regulated and how HIF-1 mediates the biological effects of hypoxia in tissues. We also summarized the latest findings concerning the role of HIF-1 in the development of HCC, which could shed light on new therapeutic approaches for the treatment of HCC.

Vascular adaptations to hypoxia: molecular and cellular mechanisms regulating vascular tone

2007 ◽  
Vol 43 ◽  
pp. 105-120 ◽  
Author(s):  
Michael L. Paffett ◽  
Benjimen R. Walker
Keyword(s):  
Vascular Tone ◽  
Cellular Proliferation ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Hypoxia Inducible Factor ◽  
Systemic Circulation ◽  
Cellular Mechanisms ◽  
Hypoxia Inducible Factor 1 ◽  
Pulmonary Vasoconstriction ◽  
Adaptive Mechanisms ◽  
Adaptive Processes

Several molecular and cellular adaptive mechanisms to hypoxia exist within the vasculature. Many of these processes involve oxygen sensing which is transduced into mediators of vasoconstriction in the pulmonary circulation and vasodilation in the systemic circulation. A variety of oxygen-responsive pathways, such as HIF (hypoxia-inducible factor)-1 and HOs (haem oxygenases), contribute to the overall adaptive process during hypoxia and are currently an area of intense research. Generation of ROS (reactive oxygen species) may also differentially regulate vascular tone in these circulations. Potential candidates underlying the divergent responses between the systemic and pulmonary circulations may include Nox (NADPH oxidase)-derived ROS and mitochondrial-derived ROS. In addition to alterations in ROS production governing vascular tone in the hypoxic setting, other vascular adaptations are likely to be involved. HPV (hypoxic pulmonary vasoconstriction) and CH (chronic hypoxia)-induced alterations in cellular proliferation, ionic conductances and changes in the contractile apparatus sensitivity to calcium, all occur as adaptive processes within the vasculature.

TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Cancer Progression ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Human Lung Cancer ◽  
Regulatory Subunit ◽  
Patients With Cancer ◽  
Hypoxia Inducible Factor 1 ◽  
Chemically Induced ◽  
Induced Tumors ◽  
Patient Prognosis

Tumor hypoxia and hypoxia-inducible factor 1 (HIF-1) activationare associated with cancer progression. Here, we demonstrate thatthe transcription factor TAp73 opposes HIF-1 activity through anontranscriptional mechanism, thus affecting tumor angiogenesis.TAp73-deficient mice have an increased incidence of spontaneousand chemically induced tumors that also display enhanced vascularization.Mechanistically, TAp73 interacts with the regulatory subunit(α) of HIF-1 and recruits mouse double minute 2 homolog intothe protein complex, thus promoting HIF-1α polyubiquitination andconsequent proteasomal degradation in an oxygen-independentmanner. In human lung cancer datasets, TAp73 strongly predictsgood patient prognosis, and its expression is associated with lowHIF-1 activation and angiogenesis. Our findings, supported by invivo and clinical evidence, demonstrate a mechanism for oxygenindependentHIF-1 regulation, which has important implicationsfor individualizing therapies in patients with cancer.

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