title: Effect of erythropoietin on mesenchymal stem cell differentiation and secretion in vitro in an acute kidney injury microenvironment.
abstract: We investigated the effect of erythropoietin (EPO) on differentiation and secretion of bone marrow-derived mesenchymal stem cells in an acute kidney injury microenvironment. Acute kidney injury mouse models were prepared. Both renal cortices were then immediately collected to produce the ischemia/reperfusion kidney homogenate supernatant. The morphological and ultrastructural changes in the cells were observed using an inverted microscope and a transmission electron microscope. Cytokeratin-18 was detected using flow cytometry. Bone morphogenetic protein-7 levels, hepatocyte growth factor, and vascular endothelial growth factor in the culture medium were detected using an enzyme-linked immunosorbent assay. The cells had high CD29 and CD44 expression, as well as low CD34 and CD45 expression. More round and oval cells with cobble-like appearances were observed after EPO treatment. In addition, an increase in the number of rough endoplasmic reticula, lysosomes, and mitochondria was observed in the cytoplasm; the intercellular junction peculiar to epithelial cells was also seen on the cell surface. After treatment with ischemia/reperfusion kidney homogenate supernatant, cytokeratin-18 expression increased significantly and EPO could magnify its expression. Bone morphogenetic protein-7 levels, hepatocyte growth factor, and vascular endothelial growth factor levels after treatment with ischemia/reperfusion kidney homogenate supernatant significantly decreased, whereas EPO increased the cytokine secretion. The acute kidney injury microenvironment can induce the bone marrow-derived mesenchymal stem cells to partially differentiate into renal tubular epithelium-shaped cells, but weaken their secretion function. EPO intervention can boost up their differentiation function and reverse their low secretion effect.
authors.affiliation: Department of Nephrology, The 455th Hospital of PLA, Shanghai, China.
authors.forename: N M
authors.initials: NM
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Tian
authors.forename: W W
authors.initials: WW
authors.lastname: Wang
authors.forename: G F
authors.initials: GF
authors.lastname: Han
authors.forename: J
authors.initials: J
authors.lastname: Cheng
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: J Y
authors.initials: JY
authors.lastname: Zhang
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy*; D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004921:Erythropoietin / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000032:analysis; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D019012:Integrin beta1 / Q000096:biosynthesis; D053538:Keratin-18 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D018952:Antigens, CD34; D055419:Bone Morphogenetic Protein 7; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D053538:Keratin-18; D042461:Vascular Endothelial Growth Factor A; C525820:bmp7 protein, mouse; C467480:vascular endothelial growth factor A, mouse; D004921:Erythropoietin; D017228:Hepatocyte Growth Factor; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse