The effects of actin cytoskeleton perturbation on keratin intermediate filament formation in mesenchymal stem/stromal cells

Tzu Hao Chang, Hsien Da Huang, Wei Kee Ong, Yun Ju Fu, Oscar K. Lee, Shu Chien, Jennifer H. Ho

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

F-actin plays a crucial role in composing the three-dimensional cytoskeleton and F-actin depolymerization alters fate choice of mesenchymal stem/stromal cells (MSCs). Here, we investigated differential gene expression and subsequent physiological changes in response to F-actin perturbation by latrunculin B in MSCs. Nineteen genes were down-regulated and 27 genes were up-regulated in the first 15min after F-actin depolymerization. Functional enrichment analysis revealed that five genes involved in keratin (KRT) intermediate filaments clustering in the chromosome 17q21.2 region, i.e., KRT14, KRT19, KRT34, KRT-associated protein (KRTAP) 1-5, and KRTAP2-3, were strongly up-regulated. Transcription factor prediction identified NKX2.5 as the potential transcription factor to control KRT19, KRT34, KRTAP1-5, and KRTAP2-3; and indeed, the protein level of NKX2.5 was markedly increased in the nuclear fraction within 15min of F-actin depolymerization. The peak of keratin intermediate filament formation was 1h after actin perturbation, and the morphological changes showed by decrease in the ratio of long-axis to short-axis diameter in MSCs was observed after 4h. Together, F-actin depolymerization rapidly triggers keratin intermediate filament formation by turning on keratin-related genes on chromosome 17q21.2. Such findings offer new insight in lineage commitment of MSCs and further scaffold design in MSC-based tissue engineering.

Original languageEnglish
Pages (from-to)3934-3944
Number of pages11
JournalBiomaterials
Volume35
Issue number13
DOIs
Publication statusPublished - Apr 2014

Keywords

  • Chromosome 17q21.2
  • F-actin depolymerization
  • Intermediate filaments
  • Keratin
  • Mesenchymal stem cells (MSCs)
  • NK2 homeobox 5 (NKX2.5)

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics
  • Medicine(all)

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