Hypoxia Modulates Fibroblastic Architecture, Adhesion and Migration: A Role for HIF-1α in Cofilin Regulation and Cytoplasmic Actin Distribution
Open Access
- 18 July 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (7), e69128
- https://doi.org/10.1371/journal.pone.0069128
Abstract
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.Keywords
This publication has 40 references indexed in Scilit:
- Hypoxia–reoxygenation‐induced endothelial barrier failure: role of RhoA, Rac1 and myosin light chain kinaseThe Journal of Physiology, 2012
- Cofilin, a hypoxia-regulated protein in murine lungs identified by 2DE: Role of the cytoskeletal protein cofilin in pulmonary hypertensionProteomics, 2012
- Cell surface dynamics – how Rho GTPases orchestrate the interplay between the plasma membrane and the cortical cytoskeletonJournal of Cell Science, 2012
- Effects of estradiol on ischemic factor-induced astrocyte swelling and AQP4 protein abundanceAmerican Journal of Physiology-Cell Physiology, 2011
- Prolyl Hydroxylase Domain (PHD) 2 Affects Cell Migration and F-actin Formation via RhoA/Rho-associated Kinase-dependent Cofilin PhosphorylationPublished by Elsevier BV ,2010
- Erythropoietin ameliorates the reduced migration of human fibroblasts during in vitro hypoxiaJournal of Physiology and Biochemistry, 2010
- ADF/Cofilin: a functional node in cell biologyTrends in Cell Biology, 2010
- Mechanics of cytokinesis in eukaryotesCurrent Opinion in Cell Biology, 2010
- HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 SensingScience, 2001
- Rho GTPases: molecular switches that control the organization and dynamics of the actin cytoskeletonPhilosophical Transactions Of The Royal Society B-Biological Sciences, 2000