Hypoxia modulates fibroblastic architecture, adhesion and migration: a role for HIF-1α in cofilin regulation and cytoplasmic actin distribution

PLoS One. 2013 Jul 18;8(7):e69128. doi: 10.1371/journal.pone.0069128. Print 2013.


Cells can adapt to hypoxia by various mechanisms. Yet, hypoxia-induced effects on the cytoskeleton-based cell architecture and functions are largely unknown. Here we present a comprehensive analysis of the architecture and function of L929 fibroblasts under hypoxic conditions (1% O2). Cells cultivated in hypoxia showed striking morphological differences as compared to cells cultivated under normoxic conditions (20% O2). These changes include an enlargement of cell area and volume, increased numbers of focal contacts and loss of cell polarization. Furthermore the β- and γ-actin distribution is greatly altered. These hypoxic adjustments are associated with enhanced cell spreading and a decline of cell motility in wound closure and single cell motility assays. As the hypoxia-inducible factor-1α (HIF-1α) is stabilised in hypoxia and plays a pivotal role in the transcriptional response to changes in oxygen availability we used an shRNA-approach to examine the role of HIF-1α in cytoskeleton-related architecture and functions. We show that the observed increase in cell area, actin filament rearrangement, decrease of single cell migration in hypoxia and the maintenance of p-cofilin levels is dependent on HIF-1α stabilisation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Depolymerizing Factors / metabolism
  • Actins / metabolism
  • Analysis of Variance
  • Animals
  • Cell Adhesion / physiology*
  • Cell Hypoxia / physiology*
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Cell Size
  • Cytoplasm / metabolism
  • Fibroblasts / cytology*
  • Fibroblasts / physiology*
  • Flow Cytometry
  • Fluorescence
  • Gene Knockdown Techniques
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Immunoblotting
  • Mice


  • Actin Depolymerizing Factors
  • Actins
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit

Grants and funding

A.Z. is a Heidenreich von Siebold fellow (http://www.med.uni-goettingen.de/de/content/forschung/182.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.