title: Hypoxic regulation of mesenchymal stem cell migration: the role of RhoA and HIF-1α.
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.
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, U.S.A.
authors.forename: Leah F
authors.initials: LF
authors.lastname: Raheja
authors.forename: Damian C
authors.initials: DC
authors.lastname: Genetos
authors.forename: Alice
authors.initials: A
authors.lastname: Wong
authors.forename: Clare E
authors.initials: CE
authors.lastname: Yellowley
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000293:Adolescent; D001854:Bone Marrow Cells / Q000166:cytology; D015687:Cell Hypoxia; D002465:Cell Movement; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020742:rhoA GTP-Binding Protein