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Biomedicines
Special Issues
Hypoxia
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Hypoxia

A special issue of Biomedicines (ISSN 2227-9059).

Deadline for manuscript submissions: closed (15 February 2018) | Viewed by 49015

Special Issue Editors

Dr. Eoin Cummins

E-Mail Website
Guest Editor
School of Medicine, UCD, Dublin, Ireland
Interests: hypoxia; hypercapnia; oxygen; carbon dioxide; inflammation; NF-kB; IBD
Dr. Carsten C. Scholz

E-Mail Website
Guest Editor
Institute of Physiology, University of Zurich, Zurich, Switzerland
Interests: hypoxia; oxygen; HIF; oxygen-sensing hydroxylases; PHDs; FIH; OTUB1; ubiquitin system; metabolism; inflammation

Special Issue Information

Dear Colleagues,

The field of hypoxia research has exploded in recent years as the importance of oxygen-sensing pathways have been implicated in physiology and disease. Much is understood in relation to the hypoxia inducible factors (HIFs) and the hydroxylase enzymes that regulate them. However, there are many areas that remain to be fully elucidated in relation to how hypoxia-dependent signalling cross talks with metabolism, cancer development and progression, inflammation and inflammatory disease. This series of reviews will focus on highlighting new emerging areas within the field of oxygen sensing and signaling, and integrating this knowledge with what is already established in the field.

Dr. Eoin Cummins
Dr. Carsten C. Scholz
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hypoxia
  • oxygen
  • HIF
  • hydroxylases
  • metabolism
  • inflammation
  • cancer

Published Papers (5 papers)

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Review

10 pages, 683 KiB  
Review
HIF Oxygen Sensing Pathways in Lung Biology
by Andrés A. Urrutia and Julián Aragonés
Biomedicines 2018, 6(2), 68; https://doi.org/10.3390/biomedicines6020068 - 06 Jun 2018
Cited by 21 | Viewed by 7077
Abstract
Cellular responses to oxygen fluctuations are largely mediated by hypoxia-inducible factors (HIFs). Upon inhalation, the first organ inspired oxygen comes into contact with is the lungs, but the understanding of the pulmonary HIF oxygen-sensing pathway is still limited. In this review we will [...] Read more.
Cellular responses to oxygen fluctuations are largely mediated by hypoxia-inducible factors (HIFs). Upon inhalation, the first organ inspired oxygen comes into contact with is the lungs, but the understanding of the pulmonary HIF oxygen-sensing pathway is still limited. In this review we will focus on the role of HIF1α and HIF2α isoforms in lung responses to oxygen insufficiency. In particular, we will discuss novel findings regarding their role in the biology of smooth muscle cells and endothelial cells in the context of hypoxia-induced pulmonary vasoconstriction. Moreover, we will also discuss recent studies into HIF-dependent responses in the airway epithelium, which have been even less studied than the HIF-dependent vascular responses in the lungs. In summary, we will review the biological functions executed by HIF1 or HIF2 in the pulmonary vessels and epithelium to control lung responses to oxygen fluctuations as well as their pathological consequences in the hypoxic lung. Full article
(This article belongs to the Special Issue Hypoxia)
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Graphical abstract

17 pages, 421 KiB  
Review
Metabolic Regulation of Hypoxia-Inducible Transcription Factors: The Role of Small Molecule Metabolites and Iron
by Peter S. J. Bailey and James A. Nathan
Biomedicines 2018, 6(2), 60; https://doi.org/10.3390/biomedicines6020060 - 17 May 2018
Cited by 29 | Viewed by 6817
Abstract
Hypoxia-inducible transcription factors (HIFs) facilitate cellular adaptations to low-oxygen environments. However, it is increasingly recognised that HIFs may be activated in response to metabolic stimuli, even when oxygen is present. Understanding the mechanisms for the crosstalk that exists between HIF signalling and metabolic [...] Read more.
Hypoxia-inducible transcription factors (HIFs) facilitate cellular adaptations to low-oxygen environments. However, it is increasingly recognised that HIFs may be activated in response to metabolic stimuli, even when oxygen is present. Understanding the mechanisms for the crosstalk that exists between HIF signalling and metabolic pathways is therefore important. This review focuses on the metabolic regulation of HIFs by small molecule metabolites and iron, highlighting the latest studies that explore how tricarboxylic acid (TCA) cycle intermediates, 2-hydroxyglutarate (2-HG) and intracellular iron levels influence the HIF response through modulating the activity of prolyl hydroxylases (PHDs). We also discuss the relevance of these metabolic pathways in physiological and disease contexts. Lastly, as PHDs are members of a large family of 2-oxoglutarate (2-OG) dependent dioxygenases that can all respond to metabolic stimuli, we explore the broader role of TCA cycle metabolites and 2-HG in the regulation of 2-OG dependent dioxygenases, focusing on the enzymes involved in chromatin remodelling. Full article
(This article belongs to the Special Issue Hypoxia)
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Graphical abstract

20 pages, 2520 KiB  
Review
Hypoxia, Metabolism and Immune Cell Function
by Ewelina Krzywinska and Christian Stockmann
Biomedicines 2018, 6(2), 56; https://doi.org/10.3390/biomedicines6020056 - 15 May 2018
Cited by 121 | Viewed by 9869
Abstract
Hypoxia is a hallmark of inflamed, infected or damaged tissue, and the adaptation to inadequate tissue oxygenation is regulated by hypoxia-inducible factors (HIFs). HIFs are key mediators of the cellular response to hypoxia, but they are also associated with pathological stress such as [...] Read more.
Hypoxia is a hallmark of inflamed, infected or damaged tissue, and the adaptation to inadequate tissue oxygenation is regulated by hypoxia-inducible factors (HIFs). HIFs are key mediators of the cellular response to hypoxia, but they are also associated with pathological stress such as inflammation, bacteriological infection or cancer. In addition, HIFs are central regulators of many innate and adaptive immunological functions, including migration, antigen presentation, production of cytokines and antimicrobial peptides, phagocytosis as well as cellular metabolic reprogramming. A characteristic feature of immune cells is their ability to infiltrate and operate in tissues with low level of nutrients and oxygen. The objective of this article is to discuss the role of HIFs in the function of innate and adaptive immune cells in hypoxia, with a focus on how hypoxia modulates immunometabolism. Full article
(This article belongs to the Special Issue Hypoxia)
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Figure 1

19 pages, 2245 KiB  
Review
Hypoxia and Chromatin: A Focus on Transcriptional Repression Mechanisms
by Michael Batie, Luis Del Peso and Sonia Rocha
Biomedicines 2018, 6(2), 47; https://doi.org/10.3390/biomedicines6020047 - 22 Apr 2018
Cited by 36 | Viewed by 7889
Abstract
Hypoxia or reduced oxygen availability has been studied extensively for its ability to activate specific genes. Hypoxia-induced gene expression is mediated by the HIF transcription factors, but not exclusively so. Despite the extensive knowledge about how hypoxia activates genes, much less is known [...] Read more.
Hypoxia or reduced oxygen availability has been studied extensively for its ability to activate specific genes. Hypoxia-induced gene expression is mediated by the HIF transcription factors, but not exclusively so. Despite the extensive knowledge about how hypoxia activates genes, much less is known about how hypoxia promotes gene repression. In this review, we discuss the potential mechanisms underlying hypoxia-induced transcriptional repression responses. We highlight HIF-dependent and independent mechanisms as well as the potential roles of dioxygenases with functions at the nucleosome and DNA level. Lastly, we discuss recent evidence regarding the involvement of transcriptional repressor complexes in hypoxia. Full article
(This article belongs to the Special Issue Hypoxia)
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Graphical abstract

13 pages, 609 KiB  
Review
VHL and Hypoxia Signaling: Beyond HIF in Cancer
by Jing Zhang and Qing Zhang
Biomedicines 2018, 6(1), 35; https://doi.org/10.3390/biomedicines6010035 - 19 Mar 2018
Cited by 78 | Viewed by 16029
Abstract
Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome [...] Read more.
Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome degradation. In recent years, emerging literature suggests that VHL also possesses other HIF-independent functions. This review will focus on VHL-mediated signaling pathways involving the latest identified substrates/binding partners, including N-Myc downstream-regulated gene 3 (NDRG3), AKT, and G9a, etc., and their physiological roles in hypoxia signaling and cancer. We will also discuss the crosstalk between VHL and NF-κB signaling. Lastly, we will review the latest findings on targeting VHL signaling in cancer. Full article
(This article belongs to the Special Issue Hypoxia)
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