title: Hypoxia modulates fibroblastic architecture, adhesion and migration: a role for HIF-1α in cofilin regulation and cytoplasmic actin distribution.
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.
authors.affiliation: Institute of Cardiovascular Physiology, University Medical Center, Georg-August-University Goettingen, Goettingen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Vogler
authors.forename: Sabine
authors.initials: S
authors.lastname: Vogel
authors.forename: Sabine
authors.initials: S
authors.lastname: Krull
authors.forename: Katja
authors.initials: K
authors.lastname: Farhat
authors.forename: Pia
authors.initials: P
authors.lastname: Leisering
authors.forename: Susanne
authors.initials: S
authors.lastname: Lutz
authors.forename: Christina M
authors.initials: CM
authors.lastname: Wuertz
authors.forename: Dörthe M
authors.initials: DM
authors.lastname: Katschinski
authors.forename: Anke
authors.initials: A
authors.lastname: Zieseniss
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D048429:Cell Size; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D005434:Flow Cytometry; D005453:Fluorescence; D055785:Gene Knockdown Techniques; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D015151:Immunoblotting; D051379:Mice
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit