HIF-1信号通路在介导DMOG动员MSCs中的作用
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国家自然科学基金(81270566);教育部高校博士点专项科研基金(20130101120022).


Mechanism of HIF-1 signaling pathway in mediating MSCs mobilization with DMOG
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    摘要:

    目的 探讨HIF-1及下游SDF-1α/CXCR4和VEGF/VEGFR 通路在介导DMOG动员MSCs中的作用机制. 方法 将雄性SD大鼠,随机分为五组:生理盐水对照组、DMOG组、YC-1组、AMD3100组、SU5416组.分别采用CFU-F法与流式细胞术检测大鼠骨髓和外周血中MSCs的数量;ELISA法检测骨髓上清及外周血清中SDF-1α及VEGF蛋白浓度;Western blotting法检测骨髓细胞中HIF-1α、SDF-1α及VEGF蛋白表达水平. 结果 同NS组比较,DMOG组CFU-Fs 数量显著增加,且CD45-CD90+细胞群比例增加(P< 0.05);同DMOG组比较,YC-1组、AMD3100组、SU5416组CFU-Fs数量均显著减少,且CD45-CD90+细胞群比例降低(P< 0.05);同DMOG组比较,YC-1组HIF-1α浓度及蛋白表达显著降低(P< 0.05),AMD3100组SDF-1α浓度及蛋白表达显著降低(P< 0.05),SU5416组VEGF浓度及蛋白表达显著降低(P< 0.05). 结论 DMOG可能通过上调HIF-1α,从而调控其下游SDF-1α/CXCR4通路与VEGF/VEGFR通路诱导MSCs 的动员.

    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 groups: Normal 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-1α and 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-1α and VEGF in BM. Results Compared with NS group, the number of CFU-Fs as well as the percentage of CD45-CD90+cells increased in DMOG group (P< 0.05); Compared with DMOG group, the number of CFU-Fs as well as the percentage of CD45-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-1α decreased significantly in YC-1 group (P< 0.05), the concentration and protein expression of SDF-1α decreased significantly in AMD3100 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-1α and activating its downstream SDF-1α/CXCR4 and VEGF/VEGFR pathway.

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胡韶君,余勤,刘丽珍,葛婷婷. HIF-1信号通路在介导DMOG动员MSCs中的作用[J].中国比较医学杂志,2015,25(1):9~14.

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  • 最后修改日期:2014-10-09
  • 在线发布日期: 2015-01-29
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