Dimethyloxalyl Glycine Regulates the HIF-1 Signaling Pathway in Mesenchymal Stem Cells.

ABSTRACT

Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewal and multidirectional differentiation capabilities. Dimethyloxalyl glycine (DMOG) mobilizes MSCs, and the hypoxia inducible factor-1 (HIF-1) signaling pathway plays an important role in MSC mobilization. We aimed to investigate the effect of DMOG on the HIF-1 pathway in MSCs. Rats were treated with DMOG, and the numbers of peripheral blood MSCs (PB-MSCs) and bone marrow MSCs (BM-MSCs) were detected by the Colony-forming unit fibroblastic (CFU-F) method. The growth curve, cell cycle and migration ability of PB-MSCs and BM-MSCs were detected by CCK-8, Flow cytometry and Transwell assays. Western blotting and real-time qPCR were used to detect the expression of the HIF-1 pathway. The number of bone marrow microvessels was detected by immunohistochemistry. DMOG significantly increased the numbers of PB-MSCs and BM-MSCs (P < 0.05). Further, the MSCs in peripheral blood and bone marrow still had the ability to proliferate and migrate after mobilization by DMOG. The expression levels of HIF-1α, stromal cell-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) in MSCs were significantly regulated by DMOG (P < 0.05). The number of bone marrow microvessels decreased after the VEGF/VEGFR signaling pathway was blocked by SU5416 (P < 0.05). Therefore, these findings demonstrated that DMOG regulates the HIF-1α signaling pathway and promotes biological effects in MSCs.