Erythropoietin expands a stromal cell population that can mediate renoprotection
Erythropoietin expands a stromal cell population that can mediate renoprotection
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DOI：
10.1152/ajprenal.90218.2008
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发表时间：
2008-10-01
影响因子：
4.2
通讯作者：
Cantley, Lloyd G.
中科院分区：
文献类型：
--
作者：
Bi, Baoyuan;Guo, Jiankan;Cantley, Lloyd G.
最近的研究表明，促红细胞生成素（EPO）受体表达于肾小管上皮细胞，EPO在体外和体内都能保护肾小管细胞免受损伤。单独的研究表明，骨髓基质细胞（MSCs）发挥肾保护作用，在缺血再灌注和顺铂肾小管损伤通过分泌的因子，减少凋亡和增加肾小管上皮细胞的增殖。在本研究中，我们证明，骨髓间充质干细胞表达EPO受体，EPO可以保护骨髓间充质干细胞从血清剥夺诱导的细胞死亡，并可以刺激骨髓间充质干细胞在体外增殖。给予小鼠EPO导致骨髓和脾脏中CD 45-Flk 1-CD 105 + MSC扩增，并动员这些细胞以及CD 45-Flk 1+内皮祖细胞进入外周循环。与以前的报告一致，EPO的给药减少了与顺铂给药相关的肾功能下降。这种效果部分再现通过腹膜内注射培养的EPO动员的细胞在顺铂处理的小鼠。因此，这些细胞的体内扩增和/或活化可能有助于EPO的肾保护作用，以保护肾小管细胞免受毒性损伤。
Recent studies have demonstrated that erythropoietin (EPO) receptors are expressed on tubular epithelial cells and that EPO can protect tubular cells from injury in vitro and in vivo. Separate studies have demonstrated that marrow stromal cells (MSCs) exert a renoprotective effect in ischemia-reperfusion and cisplatin tubular injury via the secretion of factors that reduce apoptosis and increase proliferation of tubular epithelial cells. In the present study we demonstrate that MSCs express EPO receptors and that EPO can protect MSCs from serum deprivation-induced cell death and can stimulate MSC proliferation in vitro. The administration of EPO to mice resulted in the expansion of CD45-Flk1-CD105+ MSCs in the bone marrow and in the spleen and mobilized these cells as well as CD45-Flk1 + endothelial progenitor cells into the peripheral circulation. Consistent with previous reports, the administration of EPO diminished the decline in renal function associated with cisplatin administration. This effect was partially reproduced by intraperitoneal injection of cultured EPO-mobilized cells in cisplatin-treated mice. Thus the in vivo expansion and/or activation of these cells may contribute to the renoprotective effects of EPO to protect tubular cells from toxic injury.