Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin-Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice.
Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin-Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice.
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DOI：
10.1038/srep26131
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发表时间：
2016-05-18
影响因子：
4.6
通讯作者：
Jarajapu YP
中科院分区：
文献类型：
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作者：
Vasam G;Joshi S;Jarajapu YP
糖尿病与骨髓干/祖细胞动员受损有关，骨髓干/祖细胞动员可加速缺血区域的血管化。这项研究表征了糖尿病小鼠模型中血管修复性骨髓祖细胞的动员。研究了肥胖匹配的对照或链脲佐菌素（STZ）诱导的糖尿病小鼠和具有瘦对照的db/db小鼠。通过循环Lin−Sca-1+cKit+（LSK）细胞的流式细胞计数和集落形成单位（CFU）测定评价G-CSF、AMD 3100或缺血诱导的动员。与各自的对照组相比，糖尿病持续时间较短（10-12周）的两种模型的循环WBC和LSK以及CFU均减少。STZ糖尿病病程越长（≥20周），G-CSF或AMD 3100动员能力越差（P < 0.01，n = 8）。在db/db小鼠中，G-CSF或AMD 3100的动员增加或不受影响（P < 0.05，n = 6至8）。在两种模型中，LSK细胞的增殖、迁移和缺血诱导的动员均受损。与未治疗组相比，瘦素受体拮抗剂PESLAN-1可增加WBC和LSK的G-CSF或AMD 3100动员。瘦素增加基础WBC，减少基础和AMD 3100动员的LSK细胞，对G-CSF没有影响。这些结果表明，mobilopathy是明显的STZ糖尿病，但不是在db/db小鼠。Leptin受体拮抗剂有望成为逆转糖尿病骨髓动员病的有效途径。
Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin−Sca-1+cKit+ (LSK) cells, and by colony forming unit (CFU) assay. The circulating WBCs and LSKs, and CFUs were reduced in both models with a shorter duration (10–12 weeks) of diabetes compared to their respective controls. Longer duration of STZ-diabetes (≥20 weeks) induced impairment of G-CSF- or AMD3100-mobilization (P < 0.01, n = 8). In db/db mice, mobilization by G-CSF or AMD3100 was either increased or unaffected (P < 0.05, n = 6 to 8). Proliferation, migration, and ischemia-induced mobilization, of LSK cells were impaired in both models. Leptin receptor antagonist, PESLAN-1, increased G-CSF- or AMD3100-mobilization of WBCs and LSKs, compared to the untreated. Leptin increased basal WBCs, decreased basal and AMD3100-mobilized LSK cells, and had no effect on G-CSF. These results suggest that mobilopathy is apparent in STZ-diabetes but not in db/db mice. Leptin receptor antagonism would be a promising approach for reversing diabetic bone marrow mobilopathy.