Bi Baoyuan, Guo Jiankan, Marlier Arnaud, Lin Shin Ru, Cantley Lloyd G
Yale University School of Medicine, 333 Cedar St., PO Box 208029, New Haven, CT 06510, USA.
Am J Physiol Renal Physiol. 2008 Oct;295(4):F1017-22. doi: 10.1152/ajprenal.90218.2008. Epub 2008 Jul 23.
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.
最近的研究表明，促红细胞生成素（EPO）受体在肾小管上皮细胞上表达，并且EPO在体外和体内均可保护肾小管细胞免受损伤。另外的研究表明，骨髓基质细胞（MSC）通过分泌减少细胞凋亡并增加肾小管上皮细胞增殖的因子，在缺血再灌注和顺铂诱导的肾小管损伤中发挥肾脏保护作用。在本研究中，我们证明MSC表达EPO受体，并且EPO可保护MSC免受血清剥夺诱导的细胞死亡，并能在体外刺激MSC增殖。给小鼠注射EPO导致骨髓和脾脏中CD45-Flk1-CD105+ MSC扩增，并将这些细胞以及CD45-Flk1+内皮祖细胞动员到外周循环中。与先前的报道一致，注射EPO可减轻与顺铂给药相关的肾功能下降。在顺铂处理的小鼠中腹腔注射培养的EPO动员细胞可部分重现这种效果。因此，这些细胞在体内的扩增和/或激活可能有助于EPO保护肾小管细胞免受毒性损伤的肾脏保护作用。
