Mechanism of HIF-1 signaling pathway in mediating MSCs mobilization with DMOG / 中国比较医学杂志

ABSTRACT

Objective To explore the role of HIF-1 and its downstream SDF-1α/CXCR4 and VEGF/VEGFR pathway in mediating MSC mobilization with DMOG .Methods Male SD rats were randomly divided into five groupsNormal saline control group , DMOG group, YC-1 group, AMD3100 group, SU5416 group.We used CFU-F assay and flow cytometry to determine the number of MSCs in rat bone marrow ( BM ) and peripheral blood ( PB ) in each group , respectively.The concentrations of SDF-1αand VEGF both in BM and PB serum in each group were detected by ELISA . Western blotting was used to test protein levels of HIF-1α, SDF-1αand VEGF in BM.Results Compared with NS group, the number of CFU-Fs as well as the percentage of CD 45 -CD90 +cells increased in DMOG group ( P <0.05);Compared with DMOG group, the number of CFU-Fs as well as the percentage of CD 45 -CD90 +cells decreased in YC-1 group, AMD3100 group and SU5416 group (P <0.05).Compared with DMOG group, the concentration and protein expression of HIF-1αdecreased significantly in YC-1 group ( P <0.05 ) , the concentration and protein expression of SDF-1αdecreased significantly in AMD 3100 group ( P <0.05 ) , the concentration and protein expression of VEGF decreased significantly in SU5416 group ( P <0.05 ).Conclusion DMOG can induce MSCs mobilization possibly via up-regulating the expression of HIF-1αand activating its downstream SDF-1α/CXCR4 and VEGF/VEGFR pathway .