Adriana and Luisa Castellucci Award Lecture 2001 Hypoxia Inducible Factor-1: Oxygen Regulation of Trophoblast Differentiation in Normal and Pre-eclamptic Pregnancies—A Review

Placenta ◽  
2002 ◽  
Vol 23 ◽  
pp. S47-S57 ◽  
Author(s):  
I. Caniggia ◽  
J.L. Winter
Keyword(s):  
Hypoxia Inducible Factor ◽  
Oxygen Regulation ◽  
Trophoblast Differentiation ◽  
Hypoxia Inducible Factor 1

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 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.

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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