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.
Subject(s)
Acute Kidney Injury/drug therapy , Erythropoietin/pharmacology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Reperfusion Injury/drug therapy , Animals , Antigens, CD34/biosynthesis , Bone Marrow Cells/metabolism , Bone Morphogenetic Protein 7/analysis , Cell Differentiation/drug effects , Cells, Cultured , Hepatocyte Growth Factor/analysis , Hyaluronan Receptors/biosynthesis , Integrin beta1/biosynthesis , Keratin-18/biosynthesis , Leukocyte Common Antigens/biosynthesis , Male , Mice , Mice, Inbred C57BL , Vascular Endothelial Growth Factor A/analysisABSTRACT
Thirteen derivatives of 6,7-methylenedioxy-1 (2H, 4H)-acridone were prepared. The structures of all the compounds synthesized were characterized by elemental analysis, IR and 1H NMR spectra. Compounds IIa, IIb, IId, IIe, IIf increased significantly the pain threshold using the hot-plate method.
