Hypoxic regulation of mesenchymal stem cell migration: The role of RhoA and HIF-1α

Leah F. Raheja, Damian C Genetos, Alice Wong, Clare E Yellowley-genetos

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

A variety of pathologies such as skeletal fracture, neoplasia and inflammation compromise tissue perfusion and thereby decrease tissue oxygen tension. We and others have demonstrated that hypoxia is a potent stimulant for MSC (mesenchymal stem cell) recruitment and differentiation, yet to date little research has focused on the effects of oxygen tension on MSC migration. In the present study, we examined the effects of hypoxia and the potential role of the GTPase RhoA and HIF-1α (hypoxia-inducible factor 1α) on MSC migration. Our results demonstrate that hypoxia decreases MSC migration through an HIF-1α and RhoA-mediated pathway. The active GTP-bound form of RhoA was reduced in 1% oxygen, whereas activation of RhoA under hypoxic conditions rescued migration. Furthermore, stabilization of HIF-1α under normoxic conditions attenuated cell migration similar to that of hypoxia. These results suggest that hypoxia negatively affects MSC migration by regulating activation of GTPases. These results highlight the importance of oxygen in regulating the recruitment of progenitor cells to areas of ischaemic tissue damage.

Original languageEnglish (US)
Pages (from-to)981-989
Number of pages9
JournalCell Biology International
Volume35
Issue number10
DOIs
StatePublished - Oct 1 2011

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Hypoxia-Inducible Factor 1
Mesenchymal Stromal Cells
Cell Movement
Oxygen
GTP Phosphohydrolases
Guanosine Triphosphate
Cell Differentiation
Stem Cells
Perfusion
Hypoxia
Pathology
Inflammation
Research
Neoplasms

Keywords

  • GTPase
  • Hypoxia
  • Hypoxia-inducible factor 1α (HIF-1α)
  • Mesenchymal stem cell (MSC)
  • Oxygen
  • RhoA

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hypoxic regulation of mesenchymal stem cell migration : The role of RhoA and HIF-1α. / Raheja, Leah F.; Genetos, Damian C; Wong, Alice; Yellowley-genetos, Clare E.

In: Cell Biology International, Vol. 35, No. 10, 01.10.2011, p. 981-989.

Research output: Contribution to journalArticle

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