Dipeptidyl peptidase 4 (DPP4) inhibitors(oral hypoglycemic agents)have
beneficial effects during the early stages of diabetes. In this study, we
evaluated the role of DPP4inhibitorsonthe biological functions of cultured
human endothelial progenitor cells (EPCs). After treating EPCs with the DPP4
inhibitors sitagliptin and vildagliptin, we examined the mRNA expression of
DPP4, vascular endothelial growth factor (VEGF),VEGF receptor 2
(VEGFR-2),endothelial nitric oxide synthase (eNOS), caspase-3,stromal
cell-derived factor-1 (SDF-1), chemokine (C-X-C motif) receptor 4 (CXCR4)
were measured by RT-PCR. The protein expression of SDF-1 and CXCR4 was
determined by Western blot; cell proliferation was tested by the MTT method,
and DPP4 activity was determined by a DPP4 assay. Our results revealed that
DPP4 expression and activity were inhibited following the treatment with
various doses of DPP4 inhibitors. Cell proliferation and the expression of
VEGF, VEGFR-2andeNOS were up regulated, while cell apoptosis was inhibited by
DPP4 inhibitors in a dose-dependent manner. DPP4 inhibitors activated the
SDF-1/CXCR4 signaling pathway, shown by the elevated expression of
SDF-1/CXCR4. This further proved that after the SDF-1/CXCR4 signaling pathway
was blocked by its inhibitor ADM3100, the effects of DPP4 inhibitors on the
proliferation and apoptosis, and the expression of VEGF, VEGFR-2and eNOS of
EPCs were significantly reduced. These findings suggest that DPP4 inhibitors
promote the biological functions of human EPCs by up regulating the
SDF-1/CXCR4 signaling pathway.
Melittin inhibits tumor angiogenesis modulated by endothelial progenitor cells associated with the SDF-1α/CXCR4 signaling pathway in a UMR-106 osteosarcoma xenograft mouse model
