Objectives Heparanase is an endoglycosidase involved in the cleavage of the heparin sulfate and plays important roles in tumour metastasis and angiogenesis. The purpose of the present study was to investigate the important role of heparanase in hypoxia-preconditioned bone marrow-derived mesenchymal stem cells (MSCs) induced angiogenesis.
Methods Heparanase gene knock-down and overexpression were used to detect the MSCs angiogenesis with or without hypoxia preconditioning. Moreover, in vivo experiments on rats with ligation of left anterior descending artery were performed to study the angiogenesis of heparanase-overexpressing MSCs.
Results Here we showed hypoxia-preconditioning markedly induced heparanase expression and reduced heparanase precursor expression in rat MSCs. Suramin, a heparanse inhibitor, decreased heparanase in MSCs and blocked hypoxia preconditioning-induced MSCs angiogenesis. Furthermore, heparanase knock-down impaired hypoxia preconditioning-induced MSCs angiogenesis by down-regulation of p38 phosphorylation, VEGF and flk-1 expression. While stable overexpression of heparanase activated this process in vitro and in vivo.
Conclusions In conclusion, our studies suggest that heparanse may regulate hypoxia preconditioning-induced MSCs angiogenesis through MAPK-p38 pathway.