Selective Interference Targeting of Lnk in Umbilical Cord-Derived Late Endothelial Progenitor Cells Improves Vascular Repair, Following Hind Limb Ischemic Injury, via Regulation of JAK2/STAT3 Signaling.
Stem Cells
; 33(5): 1490-500, 2015 May.
Article
de En
| MEDLINE
| ID: mdl-25537795
ABSTRACT
The Lnk adaptor protein is a strong negative regulator that affects self-renewal of hematopoietic stem cells and vascular repair in injured tissues. However, the signaling mechanisms through which these proteins influence the vascular regeneration function of endothelial progenitor cells (EPCs) remain unknown. In this study, we investigated the effect of Lnk-targeted small interfering RNA (si-lnk) on the clonogenic proliferative potential and vascular regenerative function of EPCs and the activation of the JAK/STAT3 signaling pathway. Treatment with stem cell factor (SCF) increased the clonogenic proliferation of si-lnk EPCs. Importantly, activation of the JAK2/STAT3 pathway was enhanced in SCF-sensitized si-lnk EPCs. In a hind limb model of ischemia, transplantation of si-lnk EPCs increased the blood flow ratio, capillary density, proliferation, and survival of transplanted cells, and the secretion of pivotal angiogenic cytokines at ischemic sites. These results provide strong evidence that si-lnk regulates the clonogenic proliferative potential of EPCs through the activation of the JAK2/STAT3 signaling pathway, thereby accelerating angiogenesis and promoting repair in injured hind limb ischemia. Stem Cells 2014;331490-1500.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Cordon ombilical
/
Cicatrisation de plaie
/
Transduction du signal
/
Protéines et peptides de signalisation intracellulaire
/
Progéniteurs endothéliaux
/
Membre pelvien
/
Ischémie
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Stem Cells
Année:
2015
Type de document:
Article
Pays d'affiliation:
Corée du Sud