Edinburgh Research Explorer

Exploring the HIFs, Buts and Maybes of Hypoxia Signalling in Disease: Lessons From Zebrafish Models

Research output: Contribution to journalArticle

  • Philip M. Elks
  • Stephen A. Renshaw
  • Annemarie H. Meijer
  • Sarah Walmsley
  • Fredericus J. Van Eeden

Related Edinburgh Organisations

Open Access permissions

Open

Documents

  • Download as Adobe PDF

    Rights statement: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

    Final published version, 683 KB, PDF document

    Licence: Creative Commons: Attribution (CC-BY)

http://dmm.biologists.org/content/dmm/8/11/1349.full.pdf
Original languageEnglish
Pages (from-to)1349-1360
JournalDisease Models & Mechanisms
Volume8
Issue number11
Early online date28 Oct 2015
DOIs
Publication statusPublished - 1 Nov 2015

Abstract

A low level of tissue oxygen (hypoxia) is a physiological feature of a wide range of diseases, from cancer to infection. Cellular hypoxia is sensed by oxygen sensitive hydroxylase enzymes, which regulate the protein stability of hypoxia inducible factor alpha (HIF-) transcription factors. When stabilised, HIF- binds with its cofactors to HIF responsive elements (HREs) in the promoters of target genes to co-ordinate a wide-ranging transcriptional program in response to the hypoxic environment. This year marks the twentieth anniversary of the discovery of the HIF-1 transcription factor and in recent years the HIF-mediated hypoxia response is being increasingly recognised as an important process in determining the outcome of diseases such as cancer, inflammatory disease and bacterial infections. Animal models have shed light on the roles of HIF in disease and have uncovered intricate control mechanisms that involve multiple cell-types, observations that may have been missed in simpler in vitro systems. These findings highlight the need for novel whole-organism models of disease to elucidate these complex regulatory mechanisms. In this review, we discuss recent advances in our understanding of hypoxia and HIFs in disease that have emerged from studies of zebrafish disease models. Findings from such models identify HIF as an integral player in the disease processes. They also highlight HIF pathway components, and their targets, as potential therapeutic targets against conditions that range from cancers to infectious disease.

Download statistics

No data available

ID: 22024491