Hypoxia and Hypoxia Signaling in Tissue Repair and Fibrosis

Zerina Lokmic, James Musyoka, Timothy D. Hewitson, Ian A. Darby

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

134 Citations (Scopus)


Following injury, vascular damage results in the loss of perfusion and consequent low oxygen tension (hypoxia) which may be exacerbated by a rapid influx of inflammatory and mesenchymal cells with high metabolic demands for oxygen. Changes in systemic and cellular oxygen concentrations induce tightly regulated response pathways that attempt to restore oxygen supply to cells and modulate cell function in hypoxic conditions. Most of these responses occur through the induction of the transcription factor hypoxia-inducible factor-1 (HIF-1) which regulates many processes needed for tissue repair during ischemia in the damaged tissue. HIF-1 transcriptionally upregulates expression of metabolic proteins (GLUT-1), adhesion proteins (integrins), soluble growth factors (TGF-β and VEGF), and extracellular matrix components (type I collagen and fibronectin), which enhance the repair process. For these reasons, HIF-1 is viewed as a positive regulator of wound healing and a potential regulator of organ repair and tissue fibrosis. Understanding the complex role of hypoxia in the loss of function in scarring tissues and biology of chronic wound, and organ repair will aid in the development of pharmaceutical agents that can redress the detrimental outcomes often seen in repair and scarring.

Original languageEnglish
Title of host publicationInternational Review of Cell and Molecular Biology
EditorsKwang W. Jeon
Place of PublicationUnited States
Number of pages47
ISBN (Print)9780123943071
Publication statusPublished - 2012
Externally publishedYes


  • Angiogenesis
  • Chronic wounds
  • HIF-1
  • Hypoxia
  • Tissue scars
  • Wound healing

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